Simon et al.

Supplementary information: Table of contents p.1

Supplementary material and methods p.2-4

• PoIy(I)-poly(C) Treatment • Flow Cytometry and Immunohistochemistry • Western Blotting • Quantitative RT-PCR • Fluorescence In Situ Hybridization • RNA-Seq • Exome capture • Sequencing

Supplementary Figures and Tables

Suppl. items Description pages Figure 1 Inactivation of Ezh2 affects normal thymocyte development 5 Figure 2 Ezh2 mouse leukemias express cell surface T cell 6 Figure 3 Expression of EZH2 and Hox in T-ALL 7 Figure 4 Additional mutation et deletion of modifiers in T-ALL 8 Figure 5 PRC2 expression and activity in lymphoproliferative disease 9 Figure 6 PRC2 regulatory network (String analysis) 10 Table 1 Primers and probes for detection of PRC2 genes 11 Table 2 Patient and T-ALL characteristics 12 Table 3 Statistics of RNA and DNA sequencing 13 Table 4 Mutations found in human T-ALLs (see Fig. 3D and Suppl. Fig. 4) 14 Table 5 SNP populations in analyzed human T-ALL samples 15 Table 6 List of altered genes in T-ALL for DAVID analysis 20 Table 7 List of David functional clusters 31 Table 8 List of acquired SNP tested in normal non leukemic DNA 32

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Supplementary Material and Methods

PoIy(I)-poly(C) Treatment. pIpC (GE Healthcare Lifesciences) was dissolved in endotoxin-free D-PBS (Gibco) at a concentration of 2 mg/ml. Mice received four consecutive injections of 150 μg pIpC every other day. The day of the last pIpC injection was designated as day 0 of experiment.

Flow Cytometry and Immunohistochemistry. Flow cytometric analyses were performed using BD Canto and BD FACSDiva 4.1 software (BD Pharmingen). Data were analysed using FlowJo V7. Antibodies used were: phycoerythrin (PE)-conjugated anti- CD4, allophycocyanin (APC)-conjugated anti-CD8, fluorescein isothiocyanate FITC)- conjugated anti-CD45 R (B220), FITC-conjugated anti-Ly6-G (GR1), PE-Cy5-conjugated anti-TCRβ, biotin-conjugated anti-TCR γδ (BD Biosciences); FITC-conjugated anti-Ly76 (Ter119), FITC-conjugated anti-CD11b, APC-Alexa Fluor 750-conjugated anti-CD3, and streptavidin-PE-Cy7 (eBiosciences). 5 μm tissue sections were prepared using standard histological techniques. Immunohistochemical reactions were carried out using primary rat anti-CD3 (AbD Serotec) or rabbit anti-Ki-67 (Biocare Medical) antibodies, secondary biotin-conjugated anti-rat or anti-rabbit antibodies (Vector). Location of bound antibodies was revealed using streptavidin-conjugated horseradish peroxidise and 3,3- diaminobenzidine according to the manufacturer’s instructions (Ventana Medical Systems). Sections were counterstained with hematoxylin. Images of tissue sections and the Wright stain–dyed cytospin preparations of bone marrow and spleen at 40-fold magnification were acquired using a Zeiss Axio-Imager Z1 microscope with an 40x / 1.3 Plan-Apochromat, oil, DIC objective and Canon MK2 camera fitted with LmScope adapter (Micro-Tech- Lab) and Canon EOS utility software. The resulting JPEG files were transformed into TIFF files using Adobe Photoshop version 11.

Western Blotting. Total cellular lysates were prepared by boiling cells in 1X Laemli buffer. Primary antibodies used for western blotting were anti-EZH2 (Cell Signaling Technology, 3147) and anti-α-tubulin (Cell Signaling Technology, 2144), anti-EZH1 (Abcam, 13665), anti-SUZ12 (Cell Signaling Technology, 3737); anti-Histone H3 (Abcam, AB1220), anti-Histone H3 (tri methyl K27) (Millipore, 07-449) and anti-Histone H3 (di methyl K27) (Abcam, ab24684), anti-Histone H3 (mono methyl K27) (Millipore 07- 448). Secondary anti–rabbit and anti–mouse HRP-conjugated antibodies were from SantaCruz Biotechnology.

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Quantitative RT-PCR. Total RNA from the bone marrow, spleen, and thymus of wild- type and sick Ezh2F/Δ mice was isolated using Trizol™ according to the manufacturer’s protocol (Invitrogen, CA) and treated with DNase I (Invitrogen, Carlsbad, CA) before cDNA synthesis. Reverse transcription of total RNA was performed using Superscript II- reverse Transcriptase and random hexamers according to the manufacturer’s protocol (Invitrogen). expression assays were designed using Roche Universal ProbeLibrary Assay Design software and were tested for maximum efficiency by standard curve analysis. Primer sequences and Universal ProbeLibrary numbers listed in supplementary Table 1. Reference endogenous control Taqman® assay for Gapdh (glyceraldehyde-3-phosphate dehydrogenase) was purchased from Applied Biosystems (Carlsbad, CA). analysis was performed on the ABI 7900HT Fast Real- Time PCR System (Applied Biosystems) or the Light Cycler 480 Real-Time PCR system (Roche). Reactions were performed in 384-well plates with an initial step of 3 minutes at 95˚C, followed by 40 cycles of: 5 sec at 95˚C and 30 sec at 60˚C. To determine the level of target gene expression, threshold cycle (Ct) values of target genes were normalized to endogenous control gene (Gapdh) (Ct = Ct target – Ct Gapdh). All reactions were done in triplicate and the average values were used for quantification. Total RNA from human leukemia specimens was isolated using TrizolTM according to the manufacturer’s protocol (Invitrogen). After DNase I treatment, the total RNA was reverse transcribed using random primers and MMLV-reverse transcriptase as recommended by manufacturer (Invitrogen). Taqman-based quantitative RT-PCR assays were performed in triplicate as described above. Primer and probe sequences for human qRT-PCR assays are listed in Supplementary Table 1.

Fluorescence In Situ Hybridization. Preparation of interphase nuclei from bone marrow or peripheral blood cells and fluorescence in situ hybridizations (FISH) experiments were performed using standard procedures. The following commercial probes were used to characterize the leukemic samples: Vysis LSI CDKN2A SpectrumOrange/CEP9 SpectrumGreen Probes; Vysis LSI ETV6 Dual Color Break Apart Rearrangement probe; Vysis LSI BCR/ABL ES Dual Color Translocation Probe; Vysis LSI Dual Color Break Apart Rearrangement probe (Abbott Molecular), and LPH049 TLX1 and LPH050 TLX3 Breakapart probes (Cytocell, Cambridge, UK). Bacterial artificial (BACs), RP11-1140K8, covering the EED gene at chromosomal band 11q14.2, RP11-28C14 covering the EZH2 gene at band 7q36.2, and RP11-640N20 covering the SUZ12 gene at band 17q11.2, were selected from the UCSC

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genome browser (http://genome.ucsc.edu/cgi-bin/hgGateway) and obtained from BACPAC Resources Center (Children's Hospital Oakland Research Institute, Oakland, CA; http://bacpac.chori.org/). BAC probes were labeled with Spectrum Orange-dUTP by nick translation according to manufacturer’s instructions (Abbott Molecular), denatured and hybridized on pretreated slides. Slides were incubated at 37°C for 16 hours in a humidified chamber, washed 10 seconds in 0.4X SSC/0.3% NP-40 and in 2X SSC/0.1% NP-40 solutions at 55°C and counterstained with DAPI II (Abbott Molecular). FISH signals were captured using CytoVision® software version 3.6 (Leica Microsystems). BACs were validated on normal metaphases and a 10% cut-off level for deletion (mean ± 3 SD) was established by analyzing 1500 nuclei from 5 different normal blood samples. Centromeric probes labeled with Spectrum Green were co-hybridized with the BAC located on the same (CEP 11, CEP7 or CEP17, Abbott Molecular). A minimum of 200 interphase nuclei was analyzed by two experienced observers for each leukemic sample.

RNA-Seq. Total RNA from bone marrow or blood samples (~5 million cells) was isolated using TrizolTM as recommended by the manufacturer (Invitrogen), and then further purifed using RNeasy columns (Qiagen). Sample quality was assessed using Bioanalyzer RNA Nano chips (Agilent). Transcriptome libraries were generated from 4μg total RNA using the TruSeq RNA Sample Prep Kit (v2) (Illumina) following the manufacturer’s protocols. Exome capture. Genomic DNA was extracted from bone marrow or blood samples (~5 million cells) using the DNeasy Blood and Tissue Kit as recommended by the manufacturer (Qiagen). Genomic libraries were constructed from 1μg of genomic DNA using the TruSeq DNA Sample Prep Kit (v2) (Illumina) following the manufacturer’s protocols. The DNA was sheared using a Covaris S2 instrument using the “TruSeq enrichment” settings as specified in the Illumina protocol. Target capture was done using the TruSeq Exome Enrichment Kit (Illumina) as recommended by the manufacturer. Four samples were pooled per enrichment reaction. Sequencing. Paired-end (2 x 100bp) sequencing was performed using the Illumina HiSeq2000 machine running TruSeq v3 chemistry. Cluster density was targeted at around 600-800k clusters/mm2. Two transcriptomes or a pool of four exomes were sequenced per lane.

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A B 50

6 WT Δ/Δ 40 2% 86 +- 2% 25 +- 3% 4.2+- 4% 30

20 Δ/Δ

WT Ezh2 + + 10 5 +- 2% 7 - 1% 51 - 2% 26 +- 2% Cells/thymus ( x 10 )

0 CD8 CD4

Supplementary Figure 1. Inactivation of Ezh2 affects normal thymocyte development. A) Total Δ/Δ thymocyte numbers in WT and Ezh2 mice at 12 days after pIpC treatment. Mean +- SD, n=4. B) Distribution of thymocyte subsets in WT and Ezh2Δ/Δ mice at 12 days after pIpC treatment. Note that Ezh2 inactivation leads to accumulation of immature CD4-CD8-, and disappearance of CD4+CD8+ cell populations. Numbers shown represent average proportions (mean +- SD, n=2) of CD8+, CD8+CD4+, CD4+ and CD8-CD4- thymocytes.

5 Simon et al. A BM Liver Kidney Kidney

WT

10 µm 10 µm 20 µm 10 µm

∆/∆

10 µm 10 µm 10 µm 10 µm

CD3 Ki67

Supplementary Figure 2. A) Left panels: infiltration of lymphoid cells in the bone marrow (BM), liver and kidney of sick Ezh2∆/∆ mouse visualized by immunohistochemical detection of CD3, 40X ∆/∆ magnification. Righ panels: accumulation of actively proliferating cells in the kidney of sick Ezh2 mouse visualized by immunohistochemical detection of the proliferating cell antigen Ki67, 40X magnification.

B Lin- CD3+ cells 98 1.7

WT

∆ ∆ 0.6 97 Supplementary Figure 2. B) Ezh2 / leukemias express cell surface T cell receptor (TCR) γδ.TCR expression was examined on cells isolated ∆/∆ #7 from enlarged lymph nodes of sick Ezh2 mice. Preparations from wild type thymocytes are shown as control. Lin: lineage CD45R, CD11b, Ly-6G, Ly-76. 2.1 99

#11

∆/∆ 3.7 95

#12

3.5 94

#9040

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A

03H078

Supplementary Figure 3. A) FISH analysis of leukemic specimen 03-H078 using BAC probe RP11-28C14 (red) covering EZH2 and CUL1 genes and centromeric probe (green). Representative cells with 3 copies of the BAC probe (detected in 87.5% of cells) and 2 copies of the centromeric probe.

Genes average 03H078

148395933 (wo 03H078) CUL1 B EZH2 PDIA4 ZNF786 ZNF398 chr 7 ZNF282 ZNF212 ZNF783 LOC155060 ZNF777 ZNF746 ZNF767 KRBA1 149412148

Supplementary Figure 3. B) Expression of EZH2 and neighbor genes in leukemia specimen 03H078 in which 3 copies of EZH2 were identified (see bottom panel, Fig. 3B). Note in this figure that expression of most genes found in 3 copies in this specimen is increased except for EZH2 and CUL1. Expression in normalized RPKM and color code as per Fig. 3B.

C

03H005 03H078 05H080 05H125 05H129 05H183 07H033 08H028 08H125 09H030 11H099 HOXA5 HOXA6 HOXA9 HOXA10

Supplementary Figure 3. C) 5’ HOXA gene expression in T-ALL speci- mens. Note that leukemia 07H033 shows high expression levels of the indicated 5’ HOX genes. This expression is correlated with high KDM6B and low EZH2 levels for this same specimen, shown in Fig. 3C-D. Expression in normalized RPKM and color code as per Fig. 3B.

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11H099 08H028 07H033 05H125 03H078 08H125 09H030 05H183 05H129 05H080 03H005 ARID1A BAZ2A BPTF BRD4 BRD7 BRE CABIN1 CHD4 CHD8 DNMT1 HDAC10 IDH3B JMJD1C KDM3B KDM4B KDM4C KDM4D KDM5A KDM6B MLL MLL2 * * MLL4 MLLT10 MYST1 * NCOR2 * * NSD1 PADI1 PADI2 PADI3 PADI4 Heterozygous deletion PADI6 (including more than 60 genes) PHC1 RNF40 Nonsense mutation SATB1 SCML4 Missense mutation 0 1 SETDB1 benign probably damaging SMARCA2 SRCAP * * unpredictable consequences TLK1 Acquired mutation TRRAP Germline mutation Pro-T Cortical Cortical Cortical Medullary Stage of T-ALL Pro-T Pro-T Pro-T Pro-T Pre-T Pre-T (ETP) T T T T

Supplementary Figure 4. Representation of mutations, indels and deletions found in genes associated with chromatin modification (DAVID class of chromatin modifiers). The functional effects of non-synonymous substitutions (color gradient) were predicted by the PolyPhen-2 program (http://genetics.bwh.harvard.edu/pph /data/). PRC2 and associated gene anomalies, shown in Fig. 3, are not listed.

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A Plasmocytic leukemia Lymphoproliferative syndrome Myeloma Biphenotypic CTRL Lymphoblastic leukemia T-ALL acute leukemia EED EZH1 EZH2 SUZ12 Expression levels High intermediate Low ∆Ct values 0 4 8

Supplementary Figure 5. A ) Expression of PRC2 genes in human hematological cancer specimens.The heat maps represents the average ∆Ct values of tested genes using GAPDH as an endogenous control to normalize levels of target gene expression. Hematologic cancer subtypes are shown on top, and PRC2 transcripts are identified to the right. Blue (low ∆Ct) and red color (high ∆Ct) in bar at the bottom indicate high and low gene expression levels, respectively.

B MW 03H005 03H078 03H096 05H080 05H125 05H129 05H183 08H028 08H125 09H030 11H099 (kDa) 15 H3K27me3

15 H3K27me2

15 H3K27me1

15 H3

Supplementary Figure 5. B) Western blot analysis of global histone H3 27 levels in human T-ALL. Leukemia ID# is shown on top, antibodies used for blotting are shown to the right, and the predicted molecular weights of are indicated to the left. Histone 3 levels (H3) are shown as a loading control.

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CHD4 SATB1 SETDB1

BAZ2A EZH2 JARID2 SUZ12 EED DNMT1

IDH3B

IDH1

DNMT3A KDM6B

CHD8 BPTF

MYST1 WBP7 MLL2

Binding MLLT10 MLL Expression Inhibition

Supplementary Figure 6. Known and predicted interactions between the PRC2 complex and other chromatin regulators. Interaction network based on the list of chromatin regulators shown in the Supplementary Table 7, footnote, was retrieved from the STRING database (http://string-db.org/).

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Supplementary Table 1. Primers and probes for detection of mouse and human PRC2 core components Mouse Gene symbol Forward (5'-3') Reverse (5'-3') Probe Eed aaattccacccacgagacc ggatattccataaccgtaaagca UniversalProbeLibrary #3 Ezh1 catgacccagaacttttgtgaa gacaaccaggaaagcgattc UniversalProbeLibrary #26 Ezh2 gggagagaacaatgataaagaagaa gacaccgagaatttgcttcag UniversalProbeLibrary #17 Suz12 gcaacatgggagacaattctt ttgtaatgtaggtccctgagaaaa UniversalProbeLibrary #16 Gapdh Taqman gene expression assay Mm99999915 Hprt Taqman gene expression assay Mm1545399

Human Gene Symbol Forward (5'-3') Reverse (5'-3') Probe (5'-FAM, 3'-TAMRA) EED cggccaagaagcagaagct gtatcagggcgttcagtgtttgt ctggagacgagaatgatgacgctgtcagta EZH1 tctcaggatgaggctgatcga attttgtttcctttccgagtagca tccagcttcctcttcaacctcaataatgattttg EZH2 cttataagcggaagaacacagaaaca gggtgctgggcctgcta ttaccagcatttggagggagcaaagga SUZ12 gtttatcatccaaaaggtgctaggat ttttggcctgcacacaagaa agtcgcaacggaccagttaagagaacacctat GAPDH agccacatcgctcagacac gcccaatacgaccaaatcc UniversalProbeLibrary #60

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Supplementary Table 2. Patient and disease characteristics

CDKN2A/CDKN2B TLX1 Leukemia Sampling time Age/Sex Blast cells Tissue Stage of T-ALL Karyotype TLX3 rearrangement ID# (%) deletion rearrangement

03H005 diagnosis 18/M 83 blood Medullary T 46,XY,der(14)t(14;17)(q32;q21)[12]/46,XY[12] biallelic (92%) negative negative

03H078 diagnosis 80/M 91 BM Pro-T 46,XY[20] negative negative negative

03H096 relapse (03-H005) 19/M 80 blood Medullary T 43~46,XY,-4,der(14)t(14;17)(q32;q21),-17,-19,+1~3mar[cp22] biallelic (78%) negative negative

47,XY,add(1)(q23),der(10)t(9;10)(q22;q24),-10,add(12)(p13), 05H080 diagnosis 39/M 95 BM Cortical T biallelic (88%) 99% positive cells NA -14,?del(16)(q23),+19,+1~3mar[cp7]/46,XY[13]

05H125 diagnosis 23/M 60 BM Pro-T 46,XY[14] negative negative negative

46,XY,del(9)(p12),add(9)(p12),+der(9)t(9;14)(q13;q11.2), 05H129 diagnosis 18/M 90 blood Cortical T biallelic (56%) negative negative -14[19]/46,idem,del(6)(q21)[4]/46,XY[5]

05H183 diagnosis 28/M 95 blood Cortical T NA negative 76% positive cells NA

07H033 diagnosis 43/F 90 BM Pro-T 45~48,XX,del(5)(q22q33),-6,-14,+1~3mar,inc[cp6]/46,XX[2] negative negative negative

monoallelic deletion 08H028 relapse 52/F 95 blood Pro-T NA negative negative (100%) 46,XX,t(8;14)(q24;q11)[8]/46,XX[12] monoallelic (43%), 08H125 diagnosis 24/F 91 blood Pre-T negative negative MYC rearrangement (FISH: 79.5% positive cells) biallelic (13.5%) monoallelic partial 09H030 relapse 19/F 75 BM Pre-T 45,XX,del(5)(q3?3),-13,add(17)(p11.1)[19]/46,XX[4] biallelic (49.5%) negative deletion (92.5%)

11H099 diagnosis 68/F 88 BM Pro-T (ETP-ALL) 46,XX[22] negative negative negative

Blast cells (%), percentage of blasts by morphologic analysis before Ficoll separation; BM, bone marrow; Stage of T-ALL, as described in the 2008 WHO Classification of Tumours of Haematopoietic and lymphoid tissues; ETP- ALL, sample classified as an early T-cell precursor acute lymphoblastic leukemia with CD1a neg, CD8 neg, CD5 neg, CD34 pos, CD117 pos, CD13 pos surface markers (Coustan-Smith E et al., PMID: 19147408, 2009). NA, not available, CDKN2A/CDKN2B deletion, % of cells with monoallelic and/or biallelic deletion.

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Supplementary Table 3. Efficiency of sequence acquisition and mapping Exome capture RNAseq % Mapped % Mean coverage % Mapped Mean Leukemia ID# Reads Mapped reads Reads Covered exon bp captured (X) Covered bp (2X) % genome Reads Mapped reads Reads RPKM 03H005 90262202 67481702 75% 60297801 97,1% 45,7 201419384 6,5% 172321788 124436847 72% 18,21 03H078 113856278 82842782 73% 60374666 97,2% 56,3 211930901 6,8% 197744132 142860933 72% 16,59 03H096 125643396 92112792 73% 60420625 97,3% 63,8 212991728 6,9% 201941804 154181172 76% 14,99 05H080 93742706 71849968 77% 60326327 97,2% 49,3 205507868 6,6% 230070914 173982409 76% 15,00 05H125 85583052 65586098 77% 60345164 97,2% 51,1 209787062 6,8% 264153436 194984569 74% 14,08 05H129 78242490 59495986 76% 60322514 97,2% 45,9 209479514 6,8% 234992912 178399304 76% 16,63 05H183 94864242 71364622 75% 60335974 97,2% 56,8 207154574 6,7% 176062796 125698759 71% 13,73 07H033 88012714 68106176 77% 60248873 97,0% 54,2 206265782 6,7% 184280946 139351893 76% 14,24 08H028 93494924 71452320 76% 60367701 97,2% 56,3 209576639 6,8% 157871522 121743927 77% 14,13 08H125 90564684 69147796 76% 60324589 97,2% 54,5 208035935 6,7% 155973252 118069807 76% 15,72 09H030 121659842 90909634 75% 60485930 97,4% 72,1 221109148 7,1% 212467564 166777864 78% 13,90 11H099 84976532 65808208 77% 60328367 97,2% 51,7 208708393 6,7% 227037608 172386068 76% 15,68 Average 96741922 73013174 76% 60348211 97,2% 54,8 209330577 6,8% 201243223 151072796 75% 15,24

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Supplementary Table 4 : mutations found in human T-ALLs (see Fig. 3D and Suppl. Fig. 4) Genes N Mutation (case) ARID1A 2 S1090G (08H028); R1323C (08H125) BAZ2A 1 R738Q (09H030) BPTF 1 E1658G (11H099) BRE 1 S11C (08H125) CABIN1 1 A1074V (07H033) CHD4 1 R1162W (05H125) CHD8 1 V1614L (09H030) DNM2 2 E7* (07H033); R770* (05H183) DNMT1 1 R601Q (08H125) DNMT3A 2 R882H (11H099); L547R (08H028) EP300 2 N1575S (09H030); P882R (05H129) HDAC10 2 K80E (05H080) IDH2 1 V305M (07H033) IDH3B 1 R209* (07H033) IKZF1 1 G43V (05H080) JAK3 1 Q507P (05H125) JARID2 1 V1193I (03H078) JMJD1C 1 E1925G (05H080) KDM3B 1 A5T (08H028) KDM4B 1 V1082L (05H183) KDM6B 2 K1073N (09H030); V374I (05H080) MLL 2 G3391E (08H125); T3534A (03H005) MLL2 2 D4530N (08H125); G3710R (03H005) MLL4 1 E2354K (09H030) MLLT10 1 K233R (11H099) MYST1 2 R446Q (11H099); *468W (09H030) NCOR2 2 S1995N (11H099); Q427R (05H080) R1350L (08H125); Q34*, V1599E, L1585Q (09H030); L1585P (05H183); NOTCH16 L1574P (05H129); C1692S, P401L (05H080); N280S (03H005) NRAS 1 G60E (07H033) NSD1 1 T1507M (09H030) PTEN 1 R234W (03H005) RNF40 1 P131S (11H099) SATB1 1 R395H (08H028) SETDB1 1 P529L (03H005) SRCAP 1 P1753S (11H099) TLK1 1 R299C (08H028) TP53 2 A161T (09H030); C238F (03H005) TRRAP 1 T41M (03H078)

14 HA chr11:62295361 chr11:62294309 chr9:139571430 AHNAK chr7:140373254 chr1:154570347 AHNAK AGPAT2 chr16:89211714 ADCK2 chr1:1238583 ADAR chr18:47318605 chr17:1012214 ACSF3 chr10:27044667 ACAP3 ACAA2 chr14:74754940 ABR chr16:16208799 ABI1 chr1:229694149 ABCD4 chr19:1041922 ABCC1 ABCB10 ABCA7 EN5 chr11:9286536 chr8:142170813 chr12:124093285 DENND5A chr12:113623217 DENND3 chr19:19039043 DDX55 chr19:19035109 DDX54 chr10:70737351 DDX49 chr20:3172433 DDX49 chr1:20979136 chr11:47256893 DDX21 DDRGK1 chr9:34614735 DDOST DDB2 DCTN3 chr8:104427354 chr2:158300469 DCI chr8:145150833 DCI DCAF13 chr16:69458603 CYTIP chr17:36959002 chr7:101713691 CYC1 chr6:43172498 CYB5B chr11:10800414 CWC25 CUX1 chr2:219267985 CUL9 CTR9 chr22:50316957 CTDSP1 chr20:2779455 CSK chr16:84651172 chr16:57493591 CRELD2 chr9:131094512 CPXM1 chr17:71196772 COTL1 chr17:71189266 COQ9 COQ4 chr18:72168607 COG1 chr3:32544147 chr5:175824647 COG1 CNDP2 chr12:7283287 chr15:74921333 CMTM6 CLTB chr19:45567648 CLSTN3 chr2:122187745 CLK3 chr7:150934827 CLASRP chr14:21867842 chr16:89712365 CLASP1 chr12:6697097 CHPF2 CHMP1A chr1:146737614 CHD8 chr19:4409184 chr22:47133984 CHD4 CHD1L chr9:123917145 CHAF1A chr9:123904538 CERK chr9:123902979 CEP110 chr9:123880790 CEP110 chr6:126667415 CEP110 chr2:37455014 chr16:88871894 CEP110 CENPW chr19:10678090 CEBPZ chr7:21946034 CDT1 chr22:19502488 CDKN2D chr20:3781397 chr4:15835921 CDCA7L chr5:10261764 CDC45 chr12:69991014 CDC25B CD38 chr5:68470226 CCT5 CCT2 chr6:13807220 CCNB1 chr14:91805641 CCDC90A chr11:64121209 CCDC88C chr11:64112394 chr17:38319967 chr11:3039105 CCDC88B chr11:3023261 CCDC88B CASC3 chr2:241536279 CARS chr17:76993649 CARS chr10:75574840 CAPN10 chr22:24481062 CANT1 chr9:139733365 CAMK2G chr8:146278038 CABIN1 chr7:23339020 C9orf86 chr4:57842832 C8orf33 chr3:56707653 C7orf30 chr2:101874342 C4orf14 chr2:220037608 C3orf63 chr20:34828371 C2orf29 chr1:25573151 C2orf24 chr1:109193830 C20orf4 chr1:228290213 C1orf63 chr17:74729691 C1orf59 chr17:3729129 C1orf35 chr17:79514675 C17orf95 chr17:79207795 C17orf85 chr14:24769222 C17orf70 C17orf56 chr14:91647715 C14orf21 chr14:60587934 C14orf159 chr14:60582677 chr13:39587833 C14orf135 chr13:39587813 C14orf135 chr12:7053647 C13orf23 chr12:49047912 C13orf23 chr10:73511484 chr7:16725620 C12orf57 C12orf41 chr11:116633724 C10orf54 chr19:1986633 BZW2 chr11:62457948 BUD13 chr5:891310 BTBD2 chr19:15355540 BSCL2 chr17:65908595 BRE chr12:51693021 BRD9 BRD4 chr19:50170370 BPTF chr12:57000083 chr19:49464861 BIN2 chr19:49464136 BCL2L12 BAZ2A chr8:103840813 BAX chr1:161145728 BAX chrX:40464945 B4GALT3 chr1:203691612 AZIN1 chr11:292973 ATP6AP2 chr19:10659630 ATP2B4 chr2:242610172 ATHL1 chr2:242593011 chr22:39918522 ATG4D chr22:39917960 ATG4B ATG4B chr1:1464617 ATF4 chr1:1455533 ATF4 chr2:190532225 ATAD3A chr8:17917212 ATAD3A chr9:140509398 ASNSD1 chr12:110874376 ASAH1 chr3:69153765 ARRDC1 chr3:69153645 ARPC3 chr1:27100171 ARL6IP5 chr1:27097679 ARL6IP5 ARID1A chr19:7509092 ARID1A chr12:57868427 ARHGEF18 chr1:161022247 chr16:88877979 chr13:107211797 ARHGAP9 chr3:57271542 ARHGAP30 ARGLU1 APRT chr19:33134354 APPL1 chr16:89350911 chr12:133319805 ANKRD27 chr12:133306808 ANKRD11 chr12:110841437 ANKLE2 chr2:112588975 chr17:66253082 ANKLE2 ANAPC7 chr17:18110155 chr9:117110052 ANAPC1 AMZ2 chr19:15471673 ALKBH5 AKNA AKAP8 Supplementary Table5.SNPpopulationsinanalyzedhumanT-ALLsamples

GENE chr16:2296877 chr16:2294549 chr15:75090646 chr2:28117455

SNV POSITION ...... R/C N:27//59Q:147 ...... N/K N:99//250Q:525 .....R/C N:162//352Q:969 .....S/R N:236//468Q:1340 ....R/Q N:220//437Q:1302 ...... I/L;I/L N:190//392Q:1116 ...... G/R N:79//159Q:471 ...... D/N N:164//335Q:1080 ...... E/K N:159//373Q:871 ...... R/C N:113//222Q:699 ...... R/P N:43//71Q:336 ...... M/V;M/V;M/V;M/V;M/V N ...... H/Y N:102//205Q:673 ...... N/D N:278//684Q:1307 ...... Y/C;Y/C N:189//359Q:120 ...... T/A;T/A N:187//376Q:113 ...... A/T N:462//1133Q:1909 .....R/Q N:167//348Q:1001 ...... A/T;A/T N:213//509Q:880 . R/H;R/H N:19//63Q:109 ...... Y/H N:611//1106Q:3070 .....L/P;L/P;L/P N:143//328Q: ...... S/C;S/C;S/C;S/C;S/C N:94/. . 1 ...... P/L N:130//252Q:771 ...... E/G;E/G N:111//250Q:654 ...... E/K N:420//861Q:2400 ...... P/S;P/S N:111//184Q:744 ...... R/Q N:312//649Q:1900 ...... A/T;A/T;A/T N:305//650 Q...... R/W;R/W;R/W;R/W N:633...... D/E;D/E;D/E N:75//154Q: . . M/V N:463//463Q:3070 . ....R/G N:2063//2389Q:3070 ...... E/* N:221//498Q:1117 ...... N/S;N/S N:139//259Q:913 ...... R/Q;R/Q N:247//600Q:113...... A/V;A/V N:1502//3277Q:3...... A/V;A/V;A/V N:105//243Q ...... R/Q;R/Q;R/Q N:62//144Q ...... L/S N:111//232Q:718 1 ...... S/R;S/R;S/R N:124//290Q ...... T/A N:133//264Q:762 ...... N/I N:2301//4453Q:3070 ...... Y/C N:207//433Q:1266 ...... R/C;R/C N:277//553Q:154...... S/G;S/G N:285//579Q:162 ...... L/V;L/V N:316//614Q:201 ...... R/C;R/C;R/C N:539//1199 ...... R/Q;R/Q N:152//339Q:854 ...... A/T N:1513//3115Q:3070 .....G/S;G/S N:715//1499Q:30 1 ...... H/R N:117//228Q:768 . ....T/S N:159//338Q:948 ...... V/M N:284//504Q:1941 ...... S/N N:123//274Q:698 ...... S/N;S/N N:81//168Q:485 T/M N:48//89Q:381 1 2 ...... I/T;I/T;I/T;I/T;I/T;I/T N:23 ...... E/A N:348//384Q:3070 ...... R/H N:587//1251Q:2786 N/D N:78//175Q:458 E/DN:264//630Q:1075 ...... E/D N:389//878Q:1767 .....G/D N:643//1143Q:3070 ...... R/C;R/C N:50//94Q:339 ...... L/F N:65//130Q:387 ...... E/K;E/K;E/K;E/K;E/K N:7 ...... R/C N:127//284Q:646 ...... R/W N:257//447Q:1713 ...... S/F;S/F;S/F;S/F;S/F N:60// ...... E/G N:113//235Q:658 ...... M/V;M/V;M/V;M/V;M/V N...... L/P N:30//65Q:189 ...... # ...... E/K N:137//306Q:749 ...... R/G;R/G N:120//233Q:735...... E/D N:275//526Q:1747 ...... S/F N:189//354Q:1297 ...... T/I N:890//1903Q:3070 S/F N:106//236Q:613 ...... R/H;R/H N:412//800Q:247 ...... R/H;R/H N:181//186Q:186. 1 .....H/Y N:34//63Q:205 ...... P/A N:64//137Q:431 . . 1 ...... A/V N:258//537Q:1306 R/W N:96//218Q:550 ...... V/I;V/I;V/I N:301//604Q:1 ...... S/I N:54//116Q:376 ...... R/K N:253//501Q:1536 ...... K/E;K/E N:232//460Q:133. A/V;A/V N:547//1245Q:26. 1 ...... T/M;T/M N:70//142Q:457 ....R/H;R/H N:917//2013Q:30 ...... D/A N:825//1550Q:3070 R/W N:103//218Q:657 . E/D N:323//627Q:1894 ...... A/T N:68//134Q:451 ....A/P N:82//149Q:492 ...... P/L;P/L N:233//415Q:1587 .....M/V N:200//433Q:1031 ....R/H;R/H N:377//781Q:192 ...... S/C;S/C N:540//1171Q:288 ...... R/C;R/C;R/C N:41//79Q:3 ...... R/Q N:120//230Q:765 ...... V/L;V/L N:127//261Q:784. ....R/W N:546//1202Q:2846 ...... Q/* N:99//253Q:468 ....L/F N:185//417Q:1006 ....C/Y N:98//183Q:597 ....R/P N:194//466Q:919 ...... L/S N:150//285Q:997 ...... V/I N:63//132Q:414 . ....D/V N:154//336Q:877 ...... A/V N:122//270Q:695 ...... A/V N:85//171Q:580 ...... P/T N:241//469Q:1305 ....M/L;M/L N:506//1125Q:2 ...... I/T;I/T;I/T N:61//122Q:381 ...... G/S;G/S;G/S N:43//92Q:30...... L/P;L/P N:248//546Q:1238 .....R/H N:38//87Q:247 ...... I/M N:731//1505Q:3070 I/T;I/T N:805//1672Q:3070...... R/Q N:128//268Q:795 ...... S/P N:137//302Q:822 ....R/W N:169//353Q:878 ...... R/C N:123//236Q:780 1 ...... R/Q N:147//289Q:886 .....G/V N:356//736Q:2009 ...... E/A;E/A;E/A;E/A N:103//1 ...... K/R;K/R;K/R;K/R N:46//10 R/C N:79//148Q:527 .....R/Q;R/Q;R/Q N:46//102Q .....R/H;R/H;R/H;R/H;R/H N:1 ...... A/V;A/V N:59//125Q:364 ...... G/R;G/R N:255//538Q:131...... G/R N:90//189Q:463

03H005 . . . . R/H N:96//214Q:378 S/R;S/R N:509//1075Q:298 . T/S;T/S N:3130//6396Q:30 R/Q N:171//376Q:1030 M/L N:81//194Q:476 ...... M/T N:398//841Q:1973 . . .

03H078 . . . . 1 ...... 1 ...... A/V;A/V N:687//1610Q:30 . . . R/H;R/H N:61//117Q:438 1 ...... M/V N:739//742Q:3070 1 ...... 1 ...... T/M N:88//190Q:542 N/D N:136//269Q:845 S/F N:266//515Q:1596 1 ...... E/D N:282//506Q:1756 R/C N:91//171Q:574 R/W N:150//327Q:836 R/W N:146//315Q:861 I/T;I/T N:722//1421Q:3070

03H096 R/H N:179//369Q:1015 R/G N:190//369Q:1156 Q/R N:113//241Q:637 S/L N:88//172Q:543 K/R;K/R N:165//390Q:860 R/Q;R/Q N:120//256Q:713 T/I N:82//169Q:506 E/D N:120//296Q:513 R/W N:79//158Q:521 G/D N:186//461Q:860 M/V N:382//640Q:2694 G/S;G/S N:85//160Q:557 2 ...... A/S N:102//219Q:567 . S/C N:217//369Q:1355 A/V N:158//343Q:727 .... 2 ...... 21...... 20...... 2 ...... 2 ...... E/D N:192//371Q:1133 2 ...... 2 ...... 2 ...... 2 ......

05H080 ....1 ...... 1 ...... 1 ...... S/L N:197//364Q:1232 1 ...... 1 ...... 1 ...... 1 10...... 10 10...... 1 ...... 1 ...... 1 ......

05H125 . ... 10...... 1 ...... 1 ...... 1 ...... 1 ...... 1 ...... 1 ...... 1 1 ...... 1 1 ...... 1 ...... 1 ...... 1 ......

05H129 LEUKEMIA ID# . ...1 ...... 1 10.5468...... 1 ...... 1 ...... 1 ...... 1 ...... 1 ...... 1 ...... 1 ...... 1 ...... 1 ...... 1 ...... 1 ...... 1 ......

05H183 S/C N:150//317Q:794 .. 1 ..... 10.5205..... 1 ..... 1 ..... 1 1 ...... 1 ..... 1 S/N;S/N N:17//35Q:169 ...... 1 ..... 1 ..... 1 ..... 1 ..... 1 ..... 1 ..... 1 ..... 10.5122 1 ...... 1 .....

07H033 ..2 ...... 2 ...... 1 .... 10.... 1 .... 1 1 ...... 1 .... 1 1 1 ...... 1 .... 1 ...... 1 .... 1 .... 1 .... 1 .... 1 .... 1 ...... 1 ....

08H028

08H125 ...... / :2/21Q71.104 5 17.01 251 0.49 1 . L/M N:123//251Q:721

09H030 ......

11H099 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ALL Simon 0.53 0.43 0.47 0.49 .65 11.98 59 0.46 70.47 861 0.49 13.17 0.49 154 0.47 0.49 11.96 232 0.43 0.48 133.34 3115 0.49 16.90 399 0.48 0.58 0.44 0.49 0.51 0.47 0.41 0.42 0.86 0.47 0.48 0.47 0.49 0.52 0.42 0.44 0.54 0.43 0.51 0.45 0.45 0.51 0.48 .71713.99 137 0.52 0.97 0.47 11.39 142 11.71 0.49 134 10.43 0.51 79 32.29 0.52 253 18.15 285 0.39 0.53 38.43 546 0.47 0.45 15.20 189 0.51 0.48 0.41 0.45 0.48 0.53 0.46 0.55 0.48 0.47 0.46 0.45 0.44 0.54 0.42 0.46 0.45 0.48 0.52 0.53 0.47 0.56 0.46 0.52 0.44 0.47 0.49 0.49 0.41 0.53 0.45 0.52 0.48 0.41 0.46 0.45 0.42 0.91 0.46 .63220.50 352 21.99 392 0.46 14.41 0.48 222 0.43 19.91 0.51 0.61 348 14.57 0.53 0.41 0.48 328 0.55 0.44 0.48 85.87 0.49 1499 0.48 0.45 40.55 1143 18.61 0.56 284 0.45 0.44 0.52 0.56 0.47 0.43 0.47 0.53 0.52 0.51 0.48 0.45 0.51 0.47 0.52 13.58 0.52 0.53 63 0.54 0.47 32.55 433 0.46 0.48 33.95 0.45 87 31.62 0.44 0.49 736 11.49 102 0.48 0.45 0.48 0.45 0.53 0.47 0.43 0.49 0.57 0.53 0.49 0.5 0.5 0.5 0.5 0.5 0.4 0.6 0.5 0.5 0.5 0.5 0.5 Mean Ratio ...... 514466 5 54 53 ALL 1427.5 1546.5 501.33 139.5 101.5 602.5 375.5 159.5 272.5 266.5 1254 2389 1199 1202 1125 1903 1171 1075 6396 3277 1133 1106 4453 1251 2013 1505 1550 1572 et 553 343 460 159 190 650 243 264 697 369 250 369 241 359 184 390 338 222 256 169 121 222 509 498 259 144 614 339 228 235 800 186 604 171 296 306 160 501 149 781 219 343 417 183 466 336 353 198 415 236 104 125 335 684 268 214 252 649 600 376 194 384 373 433 579 274 130 250 504 754 841 230 469 268 302 289 538 228 233 526 354 116 132 270 537 290 447 261 90 92 65 71 94 5 6 4 3 7 Mean Variant 8 1 0 7 6 Depth ALL 15 al. 144.11 255.23 255.23 149.15 150.06 44.16 34.14 28.53 35.60 10.94 13.18 12.86 11.86 44.16 12.92 19.28 12.11 40.50 15.85 13.55 47.19 12.66 17.26 10.58 11.67 29.24 32.29 14.33 13.99 13.21 11.85 21.79 14.48 38.68 20.38 20.64 12.92 35.39 42.25 55.93 10.62 14.04 12.46 26.73 26.73 17.26 39.63 12.83 16.76 63.00 14.21 21.25 20.69 11.00 18.96 12.83 16.97 11.71 27.00 24.39 29.27 75.39 25.36 22.39 18.15 18.15 52.32 16.43 12.12 11.80 76.74 17.88 19.77 24.59 12.12 22.82 83.71 52.00 14.28 12.86 22.89 17.36 16.28 21.43 20.64 28.30 11.40 29.78 16.81 35.56 14.76 45.65 28.30 34.14 28.29 10.23 18.50 28.29 36.13 40.55 55.66 20.58 19.27 21.87 19.96 12.57 11.98 24.59 32.93 15.74 23.95 40.43 19.68 10.60 33.77 18.15 23.02 44.91 11.39 21.51 59.66 14.52 11.32 14.75 11.68 59.56 16.69 16.08 11.55 RPKM ALL Simon et al.

DGCR6L chr22:20307309 ...... R/C N:189//403 Q:963 . 1 0.47 403 14.82 DGKA chr12:56332709 ...... K/R;K/R;K/R;K/R N:354//6. . . 1 0.51 693 66.50 DGKA chr12:56334185 ...... T/A;T/A;T/A;T/A N:301//6 1 0.49 616 66.50 DHPS chr19:12792381 ...... N/S;N/S;N/S N:219//487 Q. . 1 0.45 487 36.53 DHX15 chr4:24578072 . T/A N:121//243 Q:785 ...... 10.524361.02 DHX37 chr12:125450261 ...... L/P N:111//219 Q:697 1 0.51 219 12.38 DHX37 chr12:125465188 ...... V/M N:85//172 Q:515 1 0.49 172 12.38 DHX38 chr16:72139995 ...... T/M N:134//134 Q:1584 . . . 1 1 134 25.00 DIAPH1 chr5:140953453 ...... P/R;P/R N:190//367 Q:1155..... 10.52 367 64.66 DIP2A chr21:47965873 ...... P/L;P/L;P/L;P/L;P/L;P/L;P/. . 1 0.41 116 10.11 DIP2A chr21:47971564 ...... M/V;M/V;M/V N:79//147 Q..... 10.54 147 10.11 DIP2A chr21:47971652 ...... R/Q;R/Q;R/Q N:104//175 Q.... 10.59 175 10.11 DNAJA2 chr16:46998617 ...... H/P N:205//374 Q:1415 ..... 10.55 374 13.25 DNAJB12 chr10:74100836 .....G/S;G/S N:119//242 Q:738 ...... 10.49 242 11.40 DNM2 chr19:10940917 ...... 5I;5I;5I;5I;5I N:296//691 Q. . . 1 0.43 691 297.13 DNM2 chr19:10940839 . . . 1I;1I;1I;1I;1I N:194//425 Q...... 10.46 425 195.50 DNM2 chr19:10940819 ...... R/*;R/*;R/*;R/*;R/* N:154..... 10.37 414 54.21 DNM2 chr19:10828937 ...... E/*;E/*;E/*;E/*;E/* N:386/.... 10.53 731 54.21 DNMT1 chr19:10265138 ...... R/Q;R/Q N:235//442 Q:145. . 1 0.53 442 49.24 DNMT3A chr2:25467436 ...... L/R;L/R;L/R N:208//429 Q 1 0.48 429 21.18 DNMT3A chr2:25457242 ...... R/H;R/H;R/H N:646//651 Q. . . 1 0.99 651 21.18 DOCK8 chr9:446583 . I/V;I/V;I/V N:145//346 Q:7...... 10.42 346 32.03 DPF2 chr11:65113822 ....E/K N:190//479 Q:816 ...... 10.447923.81 DYM chr18:46906089 I/S N:65//138 Q:469 . I/S N:79//170 Q:532 ...... 20.47 154 15.30 DYNC1H1 chr14:102453024 ...... A/V N:141//271 Q:857 ..... 10.52 271 34.86 DYNC1LI1 chr3:32586521 ...... V/I N:161//312 Q:1073 1 0.52 312 14.23 EFTUD2 chr17:42931962 . G/R;G/R N:320//664 Q:183...... 10.48 664 31.81 EHBP1L1 chr11:65359530 . L/V N:578//1186 Q:3070 ...... 10.49 1186 27.53 EIF2A chr3:150290252 . . . P/H N:638//1307 Q:3070 ...... 10.49 1307 22.86 EIF2A chr3:150301652 ....E/A N:277//587 Q:1523 ...... 10.47 587 22.86 EIF2AK4 chr15:40326538 . . . D/E N:80//156 Q:568 ...... 10.51 156 12.88 EIF3B chr7:2419113 . . . P/L;P/L N:619//1223 Q:307...... 10.51 1223 65.71 EIF5 chr14:103803139 . . . K/*;K/* N:175//617 Q:332 ...... 10.28 617 40.59 ELAC2 chr17:12896271 .....R/T;R/T;R/T N:490//497 Q ...... 10.99 497 21.27 ENTPD6 chr20:25203612 I/T;I/T N:276//522 Q:1838 . I/T;I/T N:116//210 Q:834 ...... 20.54 366 18.12 EP300 chr22:41546030 ...... P/R N:328//669 Q:1883 . 1 0.49 669 22.61 EP300 chr22:41569733 .....N/S N:189//378 Q:1181 ...... 10.537822.61 EPS15 chr1:51868151 . A/G;A/G N:55//101 Q:437 ...... 10.54 101 12.26 ERAP1 chr5:96098915 ...... A/T N:391//496 Q:3070 ..... 10.79 496 23.07 ERP29 chr12:112460215 ...... K/R N:695//1493 Q:3070 . . . K/R N:1620//3288 Q:3070 2 0.48 2390.5 65.01 ERV3 chr7:64452458 ...... N/T N:214//476 Q:1120 . 1 0.45 476 13.22 ETV6 chr12:11992206 ....2I N:651//1310 Q:3070 ...... 10.5 1310 655.00 EVI2A chr17:29645473 . . . G/S;G/S N:313//618 Q:193 ...... 10.51 618 11.15 EXOC4 chr7:133749093 ...... V/L N:127//240 Q:867 . . 1 0.53 240 17.24 EXOSC6 chr16:70285227 ...... P/T N:101//215 Q:400 . 1 0.47 215 13.45 FAM113A chr20:2816807 . S/L N:341//698 Q:1933 ...... 10.49 698 15.46 FAM134A chr2:220046431 ...... I/L N:225//444 Q:1336 . 1 0.51 444 22.19 FAM134C chr17:40734182 ...... S/R N:83//151 Q:596 . 1 0.55 151 10.11 FAM160B2 chr8:21956096 ...... A/T N:48//97 Q:308 . . 1 0.49 97 14.28 FAM38A chr16:88782453 ...... E/K N:493//1107 Q:2582 . 1 0.45 1107 42.43 FAM38A chr16:88782988 ...... R/H N:604//1217 Q:3055 ..... 10.51217 42.43 FAM40A chr1:110592970 . S/C N:108//195 Q:781 ...... S/C N:182//328 Q:1237 . . . 2 0.55 261.5 15.29 FANCG chr9:35075598 ....R/W N:148//316 Q:904 ...... 10.47 316 12.63 FBXL6 chr8:145581780 G/R;G/R N:23//43 Q:206 . G/R;G/R N:42//73 Q:297 ...... 20.56 58 11.76 FBXL6 chr8:145581950 ...... G/A;G/A N:22//53 Q:135 ..... 10.42 53 11.76 FBXO7 chr22:32894158 ...... K/Q;K/Q N:572//1070 Q:30 1 0.53 1070 53.42 FBXW5 chr9:139835802 M/T N:682//1379 Q:3070 . M/T N:406//829 Q:2267 ...... 20.49 1104 35.84 FCGRT chr19:50017538 ....K/N;K/N N:320//555 Q:205...... 10.58 555 17.35 FDFT1 chr8:11687784 ...... D/G N:506//995 Q:3070 . . 1 0.51 995 106.94 FHOD1 chr16:67270931 ....E/D N:80//171 Q:407 ...... 10.47 171 12.56 FKBP4 chr12:2909634 ...... N/S N:399//812 Q:2051 . 1 0.49 812 29.97 FLNA chrX:153592640 ...... R/Q;R/Q N:4229//4366 Q:3. 1 0.97 4366 141.85 FOXM1 chr12:2968627 ...... P/L;P/L;P/L N:87//180 Q:5 .... 10.48 180 21.10 FOXM1 chr12:2973891 ...... R/C;R/C;R/C N:269//523 Q. 1 0.51 523 21.10 FPGS chr9:130572046 ...... A/T;A/T N:179//368 Q:805 1 0.49 368 39.69 FTH1 chr11:61732941 ...... K/R N:8532//16206 Q:3070.... 10.53 16206 790.34 FYTTD1 chr3:197503803 ...... R/Q;R/Q N:525//873 Q:307. . . 1 0.6 873 17.55 GAK chr4:877107 N/S N:197//352 Q:1301 . N/S N:219//521 Q:1010 ...... 20.49 436.5 24.47 GAR1 chr4:110743600 ...... R/Q;R/Q N:81//146 Q:594 . . 1 0.55 146 17.60 GARS chr7:30661040 ...... R/H N:300//605 Q:1765 . . 1 0.5 605 28.22 GBAS chr7:56032324 ...... A/T N:32//81 Q:133 . 1 0.4 81 16.58 GIT1 chr17:27903359 ...... G/A;G/A N:135//259 Q:828.... 10.52 259 28.32 GIT2 chr12:110434014 R/W;R/W;R/W;R/W;R/W;R. R/W;R/W;R/W;R/W;R/W;R...... 20.49 176.5 13.90 GLTSCR2 chr19:48250243 ...... P/A N:2327//4652 Q:3070 . 1 0.5 4652 390.23 GNL1 chr6:30520367 ...... E/K N:219//372 Q:1373 . . 1 0.59 372 14.57 GNPAT chr1:231402129 ...... R/Q N:63//151 Q:373 .... 10.42 151 17.75 GPATCH8 chr17:42476854 ...... R/H N:128//252 Q:817 1 0.51 252 16.18 GRAMD1A chr19:35512723 H/N;H/N N:257//507 Q:139. H/N;H/N N:253//547 Q:110...... 20.48 527 34.88 GRAMD1A chr19:35514181 ...... R/H;R/H N:550//1187 Q:22. . . 1 0.46 1187 34.88 GTF3A chr13:28004098 .....Y/H N:2253//4335 Q:3070 ...... 10.52 4335 150.99 GTF3C1 chr16:27561199 .....E/Q N:43//76 Q:341 ...... 10.57 76 13.36 HAUS1 chr18:43685199 . . . I/V N:217//409 Q:1385 ...... 10.53 409 15.82 HAUS5 chr19:36113545 ...... E/G N:142//283 Q:873 1 0.5 283 10.44 HDAC10 chr22:50688909 . . . K/E;K/E N:155//267 Q:110...... 10.58 267 17.22 HDLBP chr2:242204015 ...... T/A;T/A N:512//1109 Q:26 1 0.46 1109 30.92 HECTD1 chr14:31581629 ...... A/T N:108//238 Q:597 . . . 1 0.45 238 12.13 HEXDC chr17:80399092 ...... K/T N:204//390 Q:1282 . 1 0.52 390 20.35 HIST1H2AC chr6:26124627 . L/S N:30//63 Q:198 ...... 10.48 63 23.97 HLA-A chr6:29911916 M/V N:363//372 Q:3070 . M/V N:614//623 Q:3070 ...... M/V N:71//124 Q:362 . . 3 0.84 373 511.80 HLA-A chr6:29911947 ...... A/V N:50//58 Q:347 . . 1 0.86 58 511.80 HLA-DRA chr6:32411076 ...... R/Q N:58//111 Q:453 . . . 1 0.52 111 62.14 HM13 chr20:30154019 . . . L/F;L/F;L/F N:286//522 Q: ...... 10.55 522 24.34 HMGXB3 chr5:149391845 P/S N:39//77 Q:304 . P/S N:100//221 Q:571 ...... 20.48 149 13.23 HSD17B4 chr5:118844919 . . . R/W;R/W;R/W N:171//415...... 10.41 415 18.68 HSF1 chr8:145535785 ...... S/A N:163//362 Q:722 . . 1 0.45 362 36.88 HSP90B1 chr12:104335420 . R/H N:568//999 Q:3070 ...... 10.57 999 121.44 IARS2 chr1:220267581 ...... R/L N:87//155 Q:511 . . 1 0.56 155 18.40 ICMT chr1:6295019 ...... C/S N:66//136 Q:417 1 0.49 136 11.05 IDH2 chr15:90630398 ...... V/M N:792//1608 Q:3070 .... 10.49 1608 141.10 IDH3B chr20:2639474 ...... R/*;R/* N:200//518 Q:900 .... 10.39 518 44.53 IDUA chr4:994440 L/M N:59//134 Q:372 . L/M N:57//138 Q:313 ...... 20.43 136 10.23 IFFO1 chr12:6649716 ...... P/L;P/L;P/L N:66//152 Q:3 . . . 1 0.43 152 10.89 IFI16 chr1:158985706 ...... A/T N:197//384 Q:1115 . . . 1 0.51 384 42.61 IFNAR2 chr21:34625037 ...... T/R;T/R;T/R N:149//310 Q ..... 10.48 310 13.72 IFNGR2 chr21:34804587 . N/I N:94//171 Q:698 ...... 10.55 171 11.23 IGSF8 chr1:160062399 ...... R/W N:100//214 Q:500 .... 10.47 214 13.49 IKZF1 chr7:50367321 . . . G/V N:266//567 Q:1282 ...... 10.47 567 39.62 INF2 chr14:105179184 ...... R/Q;R/Q N:92//231 Q:410 . . . 1 0.4 231 17.10 INF2 chr14:105179237 . D/N;D/N N:354//652 Q:228...... 10.54 652 17.10 INTS1 chr7:1527000 ...... R/S N:200//381 Q:1222 . . . 1 0.52 381 38.42 IRF2BP2 chr1:234744889 ...... P/A;P/A N:99//209 Q:502 P/S;P/S N:79//149 Q:499 P/S;P/S N:366//722 Q:1827. 3 0.5 360 73.44 ITM2C chr2:231729802 ...... A/V;A/V;A/V N:69//134 Q ..... 10.51 134 103.68 ITPR2 chr12:26592174 ...... K/Q N:184//319 Q:1333 . . . 1 0.58 319 12.81 ITSN2 chr2:24426604 ...... Q/P;Q/P N:50//100 Q:349 . . 1 0.5 100 10.02 IWS1 chr2:128262678 ...... E/D N:134//298 Q:743 ..... 10.45 298 17.06 JAK3 chr19:17949121 ....Q/P N:433//1061 Q:2029 ...... 10.41 1061 19.83 JARID2 chr6:15520318 . V/I N:212//470 Q:1187 ...... 10.45 470 19.99 JMJD1C chr10:64953193 . . . E/G;E/G N:140//309 Q:810...... 10.45 309 13.51 KATNB1 chr16:57790300 L/P N:192//411 Q:1099 . L/P N:204//407 Q:1218 ...... 20.48 409 21.17 KCTD13 chr16:29937341 ...... A/V N:51//97 Q:265 . 1 0.53 97 11.39 KDM3B chr5:137688497 ...... A/T N:44//46 Q:467 . . . 1 0.96 46 17.94 KDM6B chr17:7752825 . . . K/N N:87//135 Q:659 ...... 10.64 135 13.44 KDM6B chr17:7750633 ...... V/I N:111//217 Q:681 . 1 0.51 217 13.44 KEAP1 chr19:10602601 ...... R/H;R/H N:81//172 Q:439 . 1 0.47 172 20.82 KIAA0182 chr16:85695279 ...... A/V;A/V N:199//374 Q:117.... 10.53 374 31.63 KIAA0319L chr1:35915492 ...... R/W N:144//284 Q:916 1 0.51 284 11.91 KIAA0430 chr16:15709701 ...... P/L;P/L;P/L N:161//313 Q: 1 0.51 313 13.33 KIAA0664 chr17:2600169 . P/S N:88//181 Q:559 ...... 10.49 181 14.34 KIAA0664 chr17:2605319 ...... V/M N:120//135 Q:1181 . 1 0.89 135 14.34 KIAA1147 chr7:141366203 ...... M/T N:218//392 Q:1414 . . . 1 0.56 392 15.34 KIAA2013 chr1:11983352 . E/K N:367//779 Q:1990 ...... 10.47 779 15.01 KIDINS220 chr2:8918840 . . D/N N:118//254 Q:709 ...... 10.46 254 10.86 KIF22 chr16:29811027 ...... S/T N:540//1105 Q:2726 . 1 0.49 1105 48.51 KRI1 chr19:10675630 ...... K/N N:165//375 Q:860 . 1 0.44 375 38.07 LANCL1 chr2:211336769 ...... N/S;N/S;N/S N:185//379 Q. . . 1 0.49 379 14.79 LAP3 chr4:17579155 ....G/R N:91//178 Q:597 ...... 10.51 178 21.63 LARP4B chr10:858873 ...... P/L N:59//121 Q:372 . . 1 0.49 121 11.01 LARP7 chr4:113568359 ...... E/D;E/D N:161//371 Q:839. E/D;E/D N:121//260 Q:717. . . 2 0.45 315.5 16.07 LARS chr5:145540036 ...... R/H N:140//279 Q:892 . . 1 0.5 279 25.64 LCP2 chr5:169675739 . Y/H N:282//627 Q:1494 ...... 10.45 627 54.27 LENG8 chr19:54966628 ...... A/T N:899//1955 Q:3070 ..... 10.46 1955 78.38 LIG1 chr19:48624555 .....V/M N:319//715 Q:1615 ...... 10.45 715 38.36 LPCAT3 chr12:7091863 ...... V/I N:137//261 Q:886 .... 10.52 261 14.69 LRCH4 chr7:100175010 . R/Q N:2043//2051 Q:3070 ...... 112051 40.71 LRDD chr11:802721 ...... P/T;P/T N:91//205 Q:351 . 1 0.44 205 11.99 LRPAP1 chr4:3517872 ....L/F N:697//1504 Q:3070 ...... 10.46 1504 50.10 LRWD1 chr7:102113226 ...... P/L N:148//246 Q:1051 1 0.6 246 13.57 LSG1 chr3:194371747 .....Y/H N:119//279 Q:649 ...... 10.43 279 17.12 LTA4H chr12:96429147 ...... R/C N:376//728 Q:2301 . 1 0.52 728 42.83 LTV1 chr6:144178951 ...... N/S N:218//423 Q:1440 . 1 0.52 423 23.92 MACF1 chr1:39751054 ...... L/V N:148//299 Q:887 . . 1 0.49 299 31.69 MACF1 chr1:39758439 ...... G/V N:199//403 Q:1122 1 0.49 403 31.69 MAGEF1 chr3:184429425 ...... L/S N:31//51 Q:270 . . . 1 0.61 51 13.43 MAN2A2 chr15:91456607 . I/V N:328//620 Q:1943 ...... 10.53 620 23.41 MAN2B2 chr4:6612828 . R/W N:128//254 Q:720 ...... 10.525412.29 MAP1LC3B chr16:87436678 ....T/M N:759//1500 Q:3070 ...... 10.51 1500 31.36 MAP2K2 chr19:4117584 ...... L/F N:240//529 Q:1257 .... 10.45 529 60.60 MAPKAPK2 chr1:206858647 T/A;T/A N:17//36 Q:157 . T/A;T/A N:30//54 Q:239 ...... 20.51 45 38.23 MARCH7 chr2:160604372 . . . M/V N:324//609 Q:2157 ...... 10.53 609 20.39 MARCH7 chr2:160604768 . A/T N:97//193 Q:665 ...... 10.519320.39 MAU2 chr19:19453435 ...... P/L N:233//467 Q:1387 1 0.5 467 21.05 MBOAT7 chr19:54684605 ...... V/M;V/M;V/M;V/M N:179. . . 1 0.41 438 22.33 MBTPS1 chr16:84103599 ....I/M N:248//495 Q:1462 ...... 10.549530.61 MCM3AP chr21:47686968 ...... R/H N:300//531 Q:1896 . 1 0.56 531 26.32 MDC1 chr6:30673064 ...... R/Q N:77//199 Q:343 . . 1 0.39 199 13.92 MDC1 chr6:30680124 . . . G/E N:115//234 Q:745 ...... 10.49 234 13.92 MED13L chr12:116445398 K/Q N:75//145 Q:534 . K/Q N:168//314 Q:1062 ...... 20.53 229.5 30.18

16 Simon et al.

MED16 chr19:868105 P/L N:154//297 Q:946 . P/L N:132//252 Q:836 ...... 20.52 274.5 16.72 MED25 chr19:50338843 ...... A/G N:86//154 Q:599 . . 1 0.56 154 16.77 MEN1 chr11:64573135 . . . G/D;G/D;G/D;G/D;G/D;G/ ...... 10.54 283 20.98 MFN2 chr1:12069692 ...... V/I;V/I N:94//183 Q:628 . . 1 0.51 183 21.59 MGRN1 chr16:4707267 ...... S/L;S/L;S/L;S/L N:160//36 ..... 10.44 362 11.74 MGST2 chr4:140625183 .....R/* N:132//275 Q:829 ...... 10.48 275 11.46 MIB2 chr1:1560686 ...... R/C;R/C;R/C;R/C;R/C N:5 ..... 10.52 112 12.58 MIB2 chr1:1564064 .....A/T;A/T;A/T;A/T;A/T N:6 ...... 10.57 122 12.58 MICAL1 chr6:109768627 . P/R;P/R N:1703//3287 Q:30...... 10.52 3287 41.13 MKI67IP chr2:122486076 ...... R/C N:168//372 Q:934 1 0.45 372 11.77 MKNK1 chr1:47042283 ...... R/Q;R/Q;R/Q N:111//212 Q. . 1 0.52 212 13.00 MKNK2 chr19:2039746 ...... G/S N:534//878 Q:3070 .... 10.61 878 26.27 MKRN1 chr7:140154944 ...... R/H N:353//765 Q:1654 .... 10.46 765 32.05 MKRN1 chr7:140158839 ...... M/V;M/V N:347//703 Q:17 1 0.49 703 32.05 MLF2 chr12:6861185 . R/H N:645//704 Q:3070 ...... 10.92 704 49.36 MLL chr11:118376788 G/E;G/E N:25//55 Q:200 . G/E;G/E N:79//159 Q:500 ...... 20.48 204 14.00 MLL chr11:118377216 ...... T/A;T/A N:97//204 Q:587 . . 1 0.48 107 14.00 MLL2 chr12:49424759 ...... D/N N:196//386 Q:1187 . . 1 0.51 386 21.07 MLL2 chr12:49427360 G/R N:76//137 Q:560 . G/R N:117//273 Q:626 ...... 20.49 205 21.07 MLL4 chr19:36224674 ...... E/K N:137//274 Q:810 . 1 0.5 274 13.34 MLLT10 chr10:21906135 ...... K/R;K/R N:92//181 Q:626 1 0.51 181 10.22 MOBKL2A chr19:2076944 ...... V/L N:1050//2123 Q:3070 .... 10.49 2123 18.64 MPST chr22:37420411 ...... R/H;R/H;R/H N:183//338 Q. . . 1 0.54 338 21.62 MRPL15 chr8:55047889 ...... L/V N:168//340 Q:867 . 1 0.49 340 10.15 MRPS23 chr17:55917178 . . . P/R N:134//304 Q:689 ...... 10.44 304 11.97 MRPS31 chr13:41323398 ...... W/C N:92//224 Q:494 1 0.41 224 11.52 MTDH chr8:98656894 . . . V/M N:266//520 Q:1600 ...... 10.51 520 22.30 MTG1 chr10:135209680 ...... G/A N:130//266 Q:829 . . 1 0.49 266 16.40 MTMR14 chr3:9724926 ...... D/V;D/V;D/V N:101//197 Q..... 10.51 197 18.35 MUM1 chr19:1360981 ...... A/V N:46//94 Q:328 ..... 10.49 94 10.24 MUTYH chr1:45797139 . . . R/C;R/C;R/C;R/C;R/C;R/C...... 10.418011.26 MUTYH chr1:45798269 . I/V;I/V;I/V;I/V;I/V;I/V N:1...... 10.53 198 11.26 MX2 chr21:42770896 . G/R N:49//112 Q:314 ...... 10.44 112 14.23 MYCBP2 chr13:77754281 ...... A/V N:113//222 Q:723 .... 10.51 222 18.08 MYH9 chr22:36684816 ...... R/Q N:1397//2700 Q:3070 ..... 10.52 2700 148.81 MYST1 chr16:31142313 ...... */W N:34//59 Q:302 . 1 0.58 59 22.77 NAA15 chr4:140255373 ...... K/* N:52//128 Q:325 . . . 1 0.41 128 10.50 NACA chr12:57113759 ...... P/S N:19//42 Q:170 ..... 10.45 42 74.37 NADSYN1 chr11:71193059 ...... V/M N:262//516 Q:1585 . . . 1 0.51 516 34.53 NAGK chr2:71299848 ...... G/S N:214//217 Q:2331 . . . 1 0.99 217 11.99 NAT10 chr11:34160943 ...... R/W;R/W N:169//338 Q:81. . . 1 0.5 338 18.74 NAT9 chr17:72767930 ....W/* N:128//288 Q:719 ...... 10.44 288 14.90 NBEAL2 chr3:47037253 ...... G/R N:194//387 Q:1054 . 1 0.5 387 27.72 NBEAL2 chr3:47040323 ...... T/M N:255//464 Q:1675 . 1 0.55 464 27.72 NBEAL2 chr3:47043885 E/K N:289//603 Q:1772 . E/K N:208//465 Q:1174 ...... 20.46 534 27.72 NBR1 chr17:41342693 .....V/I;V/I;V/I N:279//558 Q:1...... 10.555818.57 NCK1 chr3:136664803 ....S/T;S/T N:110//210 Q:776 ...... 10.52 210 11.69 NCOR2 chr12:124821400 ...... S/N;S/N N:97//224 Q:480 1 0.43 224 32.85 NCOR2 chr12:124911216 . . . Q/R;Q/R N:361//709 Q:220...... 10.51 709 32.85 NDST2 chr10:75566517 ...... E/D N:168//339 Q:1020 .... 10.533916.48 NFIL3 chr9:94171941 ...... S/Y N:48//118 Q:298 ..... 10.41 118 24.94 NFKB1 chr4:103451021 ....H/R;H/R N:86//196 Q:539 ...... 10.44 196 13.20 NFU1 chr2:69664523 .....A/V N:114//234 Q:438 ...... 10.49 234 10.82 NGDN chr14:23945508 .....S/T;S/T N:321//612 Q:1951...... 10.52 612 17.86 NHP2 chr5:177577923 . R/Q N:704//1535 Q:3070 ...... 10.46 1535 59.64 NIPBL chr5:36962301 .....A/T;A/T N:153//340 Q:619...... 10.45 340 14.84 NISCH chr3:52518628 ...... S/F N:133//272 Q:846 . . . 1 0.49 272 29.13 NMRAL1 chr16:4511868 .....D/E N:317//620 Q:1880 ...... 10.51 620 17.66 NMRAL1 chr16:4516301 ....A/T N:194//352 Q:1172 ...... 10.55 352 17.66 NOP58 chr2:203167758 .....P/R N:552//1196 Q:2518 ...... 10.46 1196 55.91 NOTCH1 chr9:139390732 ...... Q/* N:260//498 Q:1522 . 1 0.52 498 30.17 NOTCH1 chr9:139399347 ...... V/E N:283//548 Q:1584 . 1 0.52 548 30.17 NOTCH1 chr9:139399389 ...... L/P N:262//568 Q:1246 . . . L/Q N:256//479 Q:1437 . 2 0.5 523.5 30.17 NOTCH1 chr9:139399422 .....L/P N:120//247 Q:647 ...... 10.49 247 30.17 NOTCH1 chr9:139400299 ...... R/L N:116//212 Q:751 . . 1 0.55 212 30.17 NOTCH1 chr9:139413921 N/S N:132//233 Q:869 . N/S N:397//794 Q:2056 ...... 20.53 513.5 30.17 NPLOC4 chr17:79536062 ...... D/H N:240//497 Q:1420 . 1 0.48 497 30.45 NQO2 chr6:3010309 ...... G/R N:38//88 Q:261 . . 1 0.43 88 10.75 NSD1 chr5:176675204 ...... T/M;T/M N:105//222 Q:647. 1 0.47 222 15.10 NSFL1C chr20:1433259 ...... L/F;L/F;L/F N:420//797 Q: .... 10.53 797 14.37 NUB1 chr7:151042515 .....Y/C N:240//440 Q:1646 ...... 10.55 440 21.02 NUDT3 chr6:34256685 . . . I/V N:353//758 Q:2000 ...... 10.47 758 24.84 NUP210 chr3:13363833 . . . C/Y N:773//1607 Q:3070 ...... 10.48 1607 69.44 OGFR chr20:61436330 .....D/G N:275//603 Q:1282 ...... 10.46 603 19.98 P4HTM chr3:49042560 ...... G/V N:89//171 Q:559 . . . 1 0.52 171 10.42 PAICS chr4:57314612 .....S/C;S/C;S/C N:1085//2040 ...... 10.53 2040 39.71 PAM16 chr16:4391463 . R/Q N:239//459 Q:1412 ...... 10.52 459 12.12 PARP10 chr8:145051905 ...... A/V N:151//290 Q:830 . . 1 0.52 290 32.03 PARP10 chr8:145058731 ...... P/R N:224//451 Q:1297 . 1 0.5 451 32.03 PBXIP1 chr1:154919209 ...... R/Q N:603//1234 Q:3070 . . . 1 0.49 1234 90.78 PCM1 chr8:17793139 ...... P/H N:122//267 Q:664 . . . 1 0.46 267 21.53 PCMT1 chr6:150070895 ...... G/D N:40//66 Q:305 . 1 0.61 66 27.72 PCNT chr21:47831758 . . . A/V N:53//122 Q:223 ...... 10.43 122 13.87 PCNT chr21:47863734 ...... R/* N:101//206 Q:626 . . . 1 0.49 206 13.87 PCNX chr14:71444466 ...... T/S N:106//220 Q:638 . 1 0.48 220 10.65 PCNXL3 chr11:65387052 R/W N:43//103 Q:233 . R/W N:76//174 Q:359 ...... 20.43 138.5 12.24 PDCD11 chr10:105162878 ...... L/V N:165//295 Q:1153 . 1 0.56 295 15.90 PDCD11 chr10:105173778 ...... G/E N:106//205 Q:731 . . . 1 0.52 205 15.90 PDIA4 chr7:148716209 V/A N:213//460 Q:1241 . V/A N:235//472 Q:1475 ...... 20.48 466 29.85 PDIA6 chr2:10933251 .....R/W N:860//1737 Q:3070 ...... 10.51737 70.26 PDRG1 chr20:30534356 . I/L N:99//202 Q:657 ...... 10.49 202 14.39 PEPD chr19:34003666 ...... G/R;G/R;G/R N:49//98 Q:2. 1 0.5 98 21.49 PEX6 chr6:42935216 ...... E/K N:76//152 Q:521 ..... 10.515213.21 PFKL chr21:45741657 ...... G/R N:137//345 Q:587 . . . 1 0.4 345 37.29 PFKL chr21:45742889 . . . R/H N:332//745 Q:1582 ...... 10.45 745 37.29 PGM1 chr1:64059362 ....K/R N:97//200 Q:592 ...... 10.48 200 15.05 PGS1 chr17:76399916 ....Y/C N:178//384 Q:986 ...... 10.46 384 14.78 PHIP chr6:79787194 ...... K/Q N:157//309 Q:1014 . 1 0.51 309 14.61 PHKB chr16:47533786 ...... A/T;A/T N:166//203 Q:139. . . 1 0.82 203 11.51 PHRF1 chr11:610520 .....P/L N:78//148 Q:471 ...... 10.53 148 11.91 PI4KB chr1:151265440 ....M/K;M/K;M/K;M/K N:295...... 10.45 657 19.28 PIGT chr20:44050056 ....R/Q;R/Q;R/Q N:441//859 Q...... 10.51 859 29.61 PIK3IP1 chr22:31687065 ...... G/S;G/S N:52//95 Q:342 ..... 10.55 95 16.30 PIK3R2 chr19:18280096 ...... A/T N:25//60 Q:150 . A/T N:84//183 Q:441 . . . 2 0.44 121.5 11.82 PIKFYVE chr2:209179036 . . . R/Q N:214//413 Q:1411 ...... 10.52 413 17.17 PITPNM1 chr11:67267629 .....D/N;D/N N:192//410 Q:111...... 10.47 410 19.58 PITRM1 chr10:3182987 ...... R/H N:121//288 Q:640 ..... 10.42 288 22.72 PKN1 chr19:14568857 .....V/M;V/M N:685//1449 Q:3...... 10.47 1449 70.10 PLEC chr8:144998443 . . . A/V;A/V;A/V;A/V;A/V;A/ ...... 10.48 342 28.27 PLEC chr8:145009036 ...... R/Q;R/Q;R/Q;R/Q;R/Q;R/Q. . . 1 0.46 113 28.27 PLXND1 chr3:129289978 ...... R/C N:731//1359 Q:3070 . 1 0.54 1359 45.19 PMPCA chr9:139305140 ...... A/E N:50//102 Q:344 . 1 0.49 102 23.15 PNN chr14:39650489 ....E/K N:941//1985 Q:3070 ...... 10.47 1985 90.27 PNRC1 chr6:89790755 ...... P/T N:1018//2147 Q:3070 . 1 0.47 2147 52.41 PNRC1 chr6:89790756 ...... P/L N:1023//2161 Q:3070 . 1 0.47 2161 52.41 PNRC1 chr6:89790774 .....T/S N:188//380 Q:915 ...... 10.49 380 52.41 POLE chr12:133250232 ...... A/T N:106//199 Q:680 . . . 1 0.53 199 29.37 POLR3E chr16:22328486 ...... T/M N:135//273 Q:833 . . . 1 0.49 273 16.03 POLRMT chr19:624894 ...... Q/L N:93//177 Q:610 .... 10.53 177 13.50 PPHLN1 chr12:42840082 ...... N/T;N/T N:55//114 Q:309 1 0.48 114 12.10 PPIL2 chr22:22039143 ...... E/K;E/K;E/K N:79//178 Q: ..... 10.44 178 12.85 PPP1R15B chr1:204379758 ...... R/K N:578//1249 Q:3070 . 1 0.46 1249 28.12 PPP4C chr16:30093814 . D/N N:345//736 Q:2013 ...... 10.47 736 50.27 PPP6R2 chr22:50874873 ...... V/M N:46//118 Q:232 .... 10.39 118 25.16 PPP6R3 chr11:68377394 ....S/A;S/A;S/A;S/A;S/A;S/A ...... 10.52 913 22.82 PRDX6 chr1:173456935 ...... P/L N:892//2061 Q:3070 1 0.43 2061 64.60 PRKCSH chr19:11560135 . R/C;R/C N:2361//4691 Q:3...... 10.54691 98.12 PRNP chr20:4680447 ...... K/R;K/R;K/R;K/R;K/R N:1. . . 1 0.46 2655 31.06 PSD4 chr2:113958973 ...... R/Q N:197//507 Q:881 .... 10.39 507 38.77 PSMD9 chr12:122340955 ...... N/S N:190//430 Q:985 ..... 10.44 430 17.15 PSMF1 chr20:1145081 ...... R/H;R/H N:649//1291 Q:30 1 0.5 1291 27.30 PTEN chr10:89717676 ...... 1I N:350//487 Q:3070 ..... 10.72 487 350.64 PTEN chr10:89717675 1I N:237//299 Q:3070 . 1I N:132//186 Q:3070 ...... 20.75 242.5 56.50 PTEN chr10:89717675 R/W N:244//293 Q:2116 . R/W N:130//166 Q:999 ...... 20.81 229.5 30.30 PTPN23 chr3:47451273 . . . T/M N:64//141 Q:364 ...... 10.45 141 11.26 PTPN23 chr3:47451863 ...... G/R N:31//58 Q:230 . . 1 0.53 58 11.26 QRICH1 chr3:49094480 ...... P/T;P/T N:220//458 Q:1317. . . 1 0.48 458 29.18 R3HDM2 chr12:57648813 ...... M/V N:208//411 Q:1276 1 0.51 411 23.68 RAB4B chr19:41289962 R/C N:417//756 Q:2757 . R/C N:453//905 Q:2660 ...... 20.53 830.5 18.74 RABGGTA chr14:24737786 ...... P/A;P/A N:80//190 Q:427 . . . 1 0.42 190 10.34 RABGGTA chr14:24738856 ...... V/M;V/M N:83//184 Q:463.... 10.45 184 10.34 RALY chr20:32664917 ...... G/S;G/S N:373//657 Q:229 ..... 10.57 657 133.36 RANBP2 chr2:109383723 ...... V/A N:94//189 Q:493 1 0.5 189 14.17 RANBP2 chr2:109384749 ...... I/T N:124//312 Q:487 1 0.4 312 14.17 RAP1GDS1 chr4:99358192 . V/I;V/I;V/I;V/I;V/I;V/I N:1...... 10.44 283 15.78 RASAL3 chr19:15568123 R/W N:321//592 Q:1953 . R/W N:256//515 Q:1384 ...... 20.52 553.5 32.03 RBM15 chr1:110882103 .....S/G N:58//128 Q:342 ...... 10.45 128 15.40 RBM19 chr12:114395805 . . . M/V;M/V;M/V N:123//310...... 10.431011.16 RBM5 chr3:50147120 ...... P/L N:209//405 Q:1322 .... 10.52 405 46.49 RBM6 chr3:50005100 ...... P/L N:165//323 Q:1080 . . 1 0.51 323 36.10 RCC2 chr1:17764914 G/C;G/C N:146//340 Q:609. G/C;G/C N:244//630 Q:797...... 20.41 485 50.87 REXO1 chr19:1827010 ...... A/V N:31//67 Q:153 .... 10.46 67 11.07 REXO1 chr19:1827826 ...... P/L N:60//99 Q:413 . . . 1 0.61 99 11.07 RFWD2 chr1:176176084 ...... S/T;S/T N:40//70 Q:252 ..... 10.57 70 10.62 RHOG chr11:3848989 .....R/Q N:555//1097 Q:3070 ...... 10.51 1097 64.70 RIN3 chr14:93043795 .....E/K N:539//1092 Q:3070 ...... 10.49 1092 36.41 RIN3 chr14:93154487 ...... S/R N:311//328 Q:3070 . . 1 0.95 328 36.41 RLTPR chr16:67687128 .....H/Y N:60//118 Q:340 ...... 10.51 118 31.19 RNASEH1 chr2:3604391 . . . E/K N:165//321 Q:992 ...... 10.51 321 12.62 RNF113A chrX:119004571 ...... D/N N:58//60 Q:702 . . 1 0.97 60 15.56 RNF126 chr19:648141 . . . T/R N:413//495 Q:3070 ...... 10.83 495 25.92 RNF213 chr17:78321941 ...... R/Q N:157//327 Q:886 1 0.48 327 20.68 RNF213 chr17:78338330 . E/Q N:34//66 Q:280 ...... 10.52 66 20.68 RNF40 chr16:30774829 ...... P/S N:238//462 Q:1345 1 0.52 462 28.85 RNF44 chr5:175959148 .....R/C N:58//118 Q:310 ...... 10.49 118 30.82 RNH1 chr11:498002 . G/S;G/S;G/S;G/S;G/S;G/S;...... 10.52 2000 32.15 RNPC3 chr1:104086048 . . . N/H N:89//219 Q:440 ...... 10.41 219 12.77

17 Simon et al.

RNPC3 chr1:104086049 . . . N/T N:91//222 Q:444 ...... 10.41 222 12.77 RPL10 chrX:153628245 .....R/S N:39450//40866 Q:307...... 10.97 40866 833.12 RPL31 chr2:101622522 . . . T/N;T/N;T/N N:7927//1709...... 10.46 17090 648.62 RPL7L1 chr6:42848664 ....K/R N:145//290 Q:822 ...... 10.529013.54 RPN1 chr3:128350949 ...... S/G N:374//761 Q:2275 . 1 0.49 761 63.41 RPN1 chr3:128356845 . T/A N:354//770 Q:1997 ...... 10.46 770 63.41 RPS15 chr19:1440230 T/S N:3249//6842 Q:3070 . T/S N:1725//3778 Q:3070 ...... 20.47 5310 654.62 RPUSD3 chr3:9879867 ...... R/C;R/C N:97//207 Q:592 . . 1 0.47 207 13.52 RRM1 chr11:4139651 ...... A/V N:167//368 Q:970 . . 1 0.45 368 28.87 RRP1 chr21:45213265 R/C N:182//339 Q:1176 . R/C N:153//321 Q:850 ...... 20.51 330 16.43 RRP1 chr21:45217930 ...... G/S N:123//235 Q:778 . 1 0.52 235 16.43 S100A9 chr1:153330857 . N/S N:6831//14488 Q:3070...... 10.47 14488 450.50 SAMD1 chr19:14199282 ...... V/L N:191//366 Q:1208 . . . 1 0.52 366 24.99 SART1 chr11:65735168 P/L N:400//796 Q:2240 . P/L N:463//900 Q:2611 ...... 20.51 848 30.77 SATB1 chr3:18435976 ...... R/H;R/H;R/H N:415//851 Q. . . 1 0.49 851 24.76 SBF1 chr22:50885623 ...... P/L N:549//1041 Q:3032 . . 1 0.53 1041 36.35 SBF1 chr22:50902792 ...... Y/C N:351//674 Q:2116 . 1 0.52 674 36.35 SCNM1 chr1:151140742 ...... A/V N:183//385 Q:961 . . 1 0.48 385 24.13 SCRIB chr8:144873475 ...... P/L;P/L N:133//276 Q:821 1 0.48 276 18.19 SCRIB chr8:144875168 . P/L;P/L N:184//363 Q:1092...... 10.51 363 18.19 SCRN2 chr17:45916283 ...... G/S;G/S N:172//317 Q:106 1 0.54 317 17.56 SDCCAG3 chr9:139301880 ....D/G;D/G;D/G N:158//331 Q...... 10.48 331 13.76 SDF4 chr1:1163884 ...... R/Q;R/Q N:467//944 Q:268 1 0.49 944 40.80 SDR39U1 chr14:24909683 ....R/H N:339//791 Q:1606 ...... 10.43 791 15.24 SEC23B chr20:18506512 T/I;T/I;T/I;T/I;T/I N:86//17. T/I;T/I;T/I;T/I;T/I N:137//3...... 20.45 253 12.25 SEC24B chr4:110384603 .....F/S;F/S N:90//205 Q:535 ...... 10.44 205 10.68 SEC31B chr10:102247482 ...... G/A N:342//675 Q:2060 . 1 0.51 675 23.94 SEC31B chr10:102267198 .....L/V N:128//293 Q:698 ...... 10.44 293 23.94 SELPLG chr12:109016871 ...... L/F N:220//424 Q:1308 . 1 0.52 424 27.94 SELPLG chr12:109017044 ...... R/H N:87//213 Q:405 ..... 10.41 213 27.94 SEPT9 chr17:75398636 ...... Q/P;Q/P;Q/P;Q/P;Q/P N:18. . . 1 0.55 333 110.83 SEPT9 chr17:75478411 . V/M;V/M;V/M;V/M;V/M;V...... 10.51 4467 110.83 SERBP1 chr1:67895727 ...... V/A;V/A;V/A;V/A N:601//. . . 1 0.47 1266 31.51 SETDB1 chr1:150922939 P/L;P/L N:33//80 Q:239 . P/L;P/L N:86//175 Q:560 ...... 20.45 127.5 14.28 SETX chr9:135140020 ...... I/T N:236//476 Q:1386 1 0.5 476 14.68 SETX chr9:135204584 ...... K/E N:119//239 Q:760 . 1 0.5 239 14.68 SF1 chr11:64534720 ...... Q/R;Q/R;Q/R;Q/R;Q/R N:5. . . 1 0.54 942 107.35 SFI1 chr22:32009730 ...... R/H;R/H N:181//329 Q:116..... 10.55 329 15.98 SFRS15 chr21:33057439 ...... M/T;M/T;M/T N:135//282 . 1 0.48 282 15.76 SFSWAP chr12:132241162 ...... T/A N:120//257 Q:682 ..... 10.47 257 20.99 SH2B1 chr16:28878328 ...... R/C;R/C;R/C;R/C N:176//3 1 0.45 395 15.95 SH2D3C chr9:130511860 . R/C;R/C;R/C;R/C N:338//7...... 10.46 742 14.45 SH3TC1 chr4:8229378 .....R/W N:248//537 Q:1133 ...... 10.46 537 14.81 SH3TC1 chr4:8230023 ...... M/V N:23//55 Q:169 1 0.42 55 14.81 SKIV2L chr6:31929403 ...... T/I N:67//143 Q:381 .... 10.47 143 16.07 SLC12A9 chr7:100454796 .....G/D N:125//231 Q:750 ...... 10.54 231 11.65 SLC25A46 chr5:110082001 ...... T/N N:69//168 Q:398 .... 10.41 168 16.41 SLC35E1 chr19:16664573 . R/C N:68//144 Q:457 ...... 10.47 144 10.98 SLC39A6 chr18:33694329 ...... Q/R;Q/R N:75//158 Q:482 1 0.47 158 12.86 SLC4A2 chr7:150761700 ...... P/L;P/L;P/L;P/L N:177//37 . 1 0.47 377 15.36 SLC4A2 chr7:150764046 . R/Q;R/Q;R/Q;R/Q N:128//3...... 10.41 312 15.36 SLK chr10:105762543 ...... K/R N:84//175 Q:523 ..... 10.48 175 10.75 SMCR8 chr17:18221339 ....L/V N:160//313 Q:990 ...... 10.51 313 11.37 SMG1 chr16:18865003 .....G/D N:170//358 Q:1009 ...... 10.47 358 19.85 SMG5 chr1:156243220 A/V N:163//303 Q:1104 . A/V N:152//315 Q:924 ...... 20.51 309 34.26 SNAP47 chr1:227946805 ....P/S N:53//112 Q:359 ...... 10.47 112 10.13 SON chr21:34922515 ....M/I;M/I N:1309//2757 Q:30...... 10.47 2757 61.85 SORL1 chr11:121440937 F/L N:44//76 Q:377 . F/L N:127//281 Q:738 ...... 20.52 178.5 24.15 SORL1 chr11:121458848 ...... F/I N:170//311 Q:1085 . . 1 0.55 311 24.15 SPAG5 chr17:26905104 . N/T N:55//102 Q:443 ...... 10.54 102 14.14 SPEN chr1:16259915 ...... P/S N:221//494 Q:1163 . 1 0.45 494 22.85 SPG11 chr15:44865000 ...... N/S;N/S N:105//220 Q:689 . 1 0.48 220 12.95 SPN chr16:29676179 ...... V/A;V/A N:330//636 Q:182..... 10.52 636 49.53 SPNS1 chr16:28986603 .....Q/R;Q/R;Q/R;Q/R N:65//1 ...... 10.58 112 17.68 SPNS3 chr17:4391185 ...... P/R N:290//639 Q:1282 ..... 10.45 639 32.26 SPRY2 chr13:80911782 ....D/A N:992//2169 Q:3070 ...... 10.46 2169 13.90 SRCAP chr16:30736002 ...... P/S N:279//535 Q:1615 1 0.52 535 23.93 SREK1 chr5:65474560 N/S;N/S N:185//344 Q:132 . N/S;N/S N:179//342 Q:120 ...... 20.53 343 23.31 SRSF2IP chr12:46320453 ...... N/D N:295//543 Q:1963 1 0.54 543 17.88 STAT5B chr17:40359729 ...... N/H N:1208//1216 Q:3070 . . . 1 0.99 1216 54.79 STK11IP chr2:220470710 D/N N:78//189 Q:436 . D/N N:112//294 Q:521 ...... 20.4241.5 17.23 STK38 chr6:36489552 ...... M/V N:207//425 Q:1213 . 1 0.49 425 21.33 STT3B chr3:31617911 ...... H/R N:1218//2389 Q:3070 . 1 0.51 2389 110.13 STT3B chr3:31621367 ...... V/I N:653//1370 Q:3070 ..... 10.48 1370 110.13 SYMPK chr19:46332271 ...... R/C N:149//306 Q:892 .... 10.49 306 33.51 TALDO1 chr11:758982 ...... D/V N:699//1328 Q:3070 .... 10.53 1328 103.27 TAP2 chr6:32800577 .....A/T N:273//486 Q:1704 ...... 10.56 486 16.16 TAP2 chr6:32802938 ...... R/H N:312//562 Q:1837 . 1 0.56 562 16.16 TARS chr5:33448792 .....A/E N:285//609 Q:1653 ...... 10.47 609 29.10 TAX1BP3 chr17:3567049 ...... L/P N:165//303 Q:987 . . . 1 0.54 303 18.70 TBL3 chr16:2025080 ...... D/N N:113//222 Q:672 . . 1 0.51 222 15.08 TBL3 chr16:2025587 ...... P/L N:93//193 Q:523 . . 1 0.48 193 15.08 TCF12 chr15:57384063 ...... T/I;T/I;T/I;T/I N:73//152 Q . . . 1 0.48 152 21.71 TCF3 chr19:1619323 ...... A/T;A/T N:410//780 Q:228. 1 0.53 780 46.59 TCF3 chr19:1621926 .....S/F;S/F N:555//1115 Q:307...... 10.51115 46.59 TELO2 chr16:1545589 . V/A N:89//173 Q:588 ...... 10.51 173 13.54 TIMM44 chr19:7997576 .....P/Q N:190//332 Q:1241 .....P/Q N:160//307 Q:997 2 0.55 319.5 13.57 TIMM44 chr19:8003040 ...... G/S N:83//153 Q:615 . . 1 0.54 153 13.57 TJAP1 chr6:43473025 ...... R/Q;R/Q;R/Q;R/Q;R/Q;R/Q.... 10.45 127 12.13 TKT chr3:53267183 ....R/Q;R/Q N:2013//4190 Q:3...... 10.48 4190 112.23 TKT chr3:53269028 ....D/E;D/E N:1354//3102 Q:3...... 10.44 3102 112.23 TLK1 chr2:171906409 ...... R/C;R/C;R/C N:147//331 Q. . . 1 0.44 331 10.98 TM9SF3 chr10:98346579 ....P/L N:136//296 Q:681 ...... 10.46 296 18.41 TMC6 chr17:76120658 ...... A/T;A/T N:241//598 Q:778. 1 0.4 598 36.66 TMC6 chr17:76121239 . R/Q;R/Q N:68//134 Q:474 ...... 10.51 134 36.66 TMEM131 chr2:98373842 ...... V/D N:168//302 Q:998 1 0.56 302 10.59 TMEM131 chr2:98543945 . . . V/I N:65//136 Q:415 ...... 10.48 136 10.59 TMEM131 chr2:98612088 ...... T/N N:39//71 Q:283 . . . 1 0.55 71 10.59 TNFAIP3 chr6:138201240 ...... T/P N:2697//5431 Q:3070 . 1 0.5 5431 124.31 TNPO3 chr7:128612584 ...... I/V;I/V N:159//333 Q:905 . 1 0.48 333 15.36 TNRC18 chr7:5428706 ....R/H N:126//153 Q:980 ...... 10.82 153 18.21 TP53 chr17:7577568 ...... C/F;C/F;C/F;C/F;C/F;C/F;C. 1 0.57 496 30.14 TP53 chr17:7578449 A/T;A/T;A/T;A/T;A/T;A/T. A/T;A/T;A/T;A/T;A/T;A/T...... 20.5545.5 30.14 TPRA1 chr3:127298917 ....S/G;S/G;S/G N:155//308 Q....S/G;S/G;S/G N:40//97 Q:26. . 2 0.46 202.5 11.05 TRAF3IP3 chr1:209933608 ...... E/G N:271//561 Q:1620 . 1 0.48 561 40.32 TRAP1 chr16:3716010 ...... R/W N:65//67 Q:742 . . . 1 0.97 67 13.75 TRIM22 chr11:5727831 ...... I/T;I/T N:431//841 Q:2608 . 1 0.51 841 30.55 TRIM22 chr11:5730685 ...... F/C;F/C N:118//260 Q:680 . . 1 0.45 260 30.55 TRIM22 chr11:5730705 ....R/C;R/C N:536//536 Q:307...... 1153630.55 TRIM56 chr7:100732397 .....R/C N:72//156 Q:416 ...... 10.46 156 10.04 TRMT2A chr22:20103876 ...... R/H;R/H N:106//193 Q:681..... 10.55 193 14.80 TRMT2A chr22:20103916 . R/C;R/C N:314//593 Q:197...... 10.53 593 14.80 TSEN54 chr17:73512643 . M/T N:36//85 Q:178 ...... 10.42 85 40.30 TSEN54 chr17:73519758 ...... S/C N:231//460 Q:1343 . . 1 0.5 460 40.30 TSPYL4 chr6:116574135 ...... R/Q N:156//349 Q:875 . . . 1 0.45 349 18.20 TSSC4 chr11:2424090 T/M N:294//575 Q:1756 . T/M N:277//548 Q:1609 ...... 20.51 561.5 24.33 TTC19 chr17:15903308 ...... P/L N:57//119 Q:307 1 0.48 119 17.47 TTC37 chr5:94876410 ...... N/S N:244//477 Q:1602 . 1 0.51 477 16.70 TTC38 chr22:46685754 ...... A/V N:46//104 Q:302 . 1 0.44 104 10.98 TUBGCP2 chr10:135099030 ...... A/T N:184//347 Q:1137 1 0.53 347 26.51 TUBGCP6 chr22:50658442 ...... P/S N:131//280 Q:753 . . 1 0.47 280 23.99 TUBGCP6 chr22:50659598 G/R N:175//387 Q:853 . G/R N:235//493 Q:1154 ...... 20.46 440 23.99 TXNDC11 chr16:11785583 ....D/G N:115//265 Q:647 ...... 10.43 265 15.02 U2AF1L4 chr19:36234727 ...... G/V N:52//108 Q:334 . 1 0.48 108 10.22 UBAP1 chr9:34241426 ...... V/L;V/L;V/L;V/L;V/L N:2 1 0.54 425 16.12 UBAP2L chr1:154226521 S/G;S/G N:278//529 Q:169 . S/G;S/G N:348//780 Q:175 ...... 20.49 654.5 31.43 UBE2M chr19:59068485 . S/I N:385//811 Q:2113 ...... 10.47 811 33.53 UBE2O chr17:74401602 ...... R/Q N:106//216 Q:680 . . 1 0.49 216 14.78 UBE2Q1 chr1:154530774 ...... A/S N:101//173 Q:603 . . 1 0.58 173 21.57 UBE3A chr15:25616729 . A/T;A/T;A/T N:25//72 Q:1 . A/T;A/T;A/T N:216//423 Q...... A/T;A/T;A/T N:143//307 Q 3 0.44 267.33 15.97 UBE4B chr1:10228220 ....Q/H;Q/H N:183//375 Q:107...... 10.49 375 10.73 UBQLN1 chr9:86292683 .....G/V;G/V N:382//871 Q:184.....G/V;G/V N:423//941 Q:220 2 0.44 906 41.13 UBQLN2 chrX:56591325 ...... S/I N:185//185 Q:2232 ..... 1118512.70 UBR4 chr1:19503178 ...... G/V N:161//344 Q:841 . 1 0.47 344 24.40 UBR4 chr1:19528302 ...... E/K N:121//267 Q:705 .... 10.45 267 24.40 UGGT1 chr2:128934411 P/L N:15//39 Q:109 . P/L N:59//119 Q:395 ...... 20.44 79 10.46 ULK1 chr12:132394378 ...... T/I N:65//114 Q:501 . . 1 0.57 114 16.78 ULK1 chr12:132399898 ...... R/Q N:74//167 Q:433 . 1 0.44 167 16.78 UNC13D chr17:73830182 ...... V/I N:316//645 Q:1766 . 1 0.49 645 47.18 UNC45A chr15:91478589 . R/Q N:37//84 Q:254 ...... 10.44 84 20.53 UQCRFS1 chr19:29703961 ...... V/G N:86//157 Q:27 . . 1 0.55 157 48.51 USP19 chr3:49145921 R/Q;R/Q N:58//142 Q:289 . R/Q;R/Q N:73//178 Q:327 ...... 20.41 160 15.57 USP19 chr3:49149151 ....S/F;S/F;S/F;S/F N:178//350...... 10.51 350 15.57 USP3 chr15:63796981 ...... D/N N:42//101 Q:262 . . . 1 0.42 101 12.08 USP34 chr2:61415378 L/F N:265//514 Q:1766 . L/F N:274//584 Q:1612 ...... 20.49 549 21.07 USP34 chr2:61552588 ....S/G N:181//344 Q:1202 ...... 10.53 344 21.07 USP36 chr17:76831394 . N/S N:97//231 Q:553 ...... 10.42 231 17.37 USP4 chr3:49365133 ...... P/T;P/T N:203//374 Q:1340. 1 0.54 374 26.61 USP48 chr1:22030875 ...... I/L N:77//157 Q:533 .... 10.49 157 15.33 UTP18 chr17:49371294 . . . N/D N:146//317 Q:834 ...... 10.46 317 19.69 VAT1 chr17:41170164 ....G/R N:428//853 Q:2412 ...... 10.585394.27 VAV3 chr1:108152557 P/T;P/T N:82//141 Q:631 . P/T;P/T N:56//137 Q:333 ...... 20.513914.61 VAV3 chr1:108185282 ...... V/I;V/I N:165//409 Q:785 .... 10.440914.61 VPS39 chr15:42492125 H/Q N:88//146 Q:682 . H/Q N:91//189 Q:572 ...... 20.54 167.5 23.45 VPS45 chr1:150054896 ...... R/W N:52//114 Q:353 . . 1 0.46 114 11.22 VRK3 chr19:50498127 ...... V/I;V/I N:81//173 Q:516 . . . 1 0.47 173 22.11 WBP11 chr12:14943486 ....P/S N:407//843 Q:1963 ...... 10.48 843 42.34 WDR46 chr6:33248507 ...... F/S;F/S N:120//290 Q:606 . 1 0.41 290 19.93 WDR48 chr3:39108050 ....S/A N:113//236 Q:710 ...... 10.48 236 18.21 WDR85 chr9:140450001 ...... R/Q N:153//327 Q:848 .... 10.47 327 15.41 WIZ chr19:15535690 ....R/Q N:155//323 Q:729 ...... 10.48 323 10.66 XPC chr3:14199940 ....K/N;K/N N:107//215 Q:663...... 10.521510.55 XPO5 chr6:43515346 .....R/Q N:276//529 Q:1731 ...... 10.52 529 11.40 XYLT1 chr16:17564337 ....R/Q N:121//246 Q:725 ...... 10.49 246 12.84 YRDC chr1:38269632 ...... Y/H N:122//257 Q:713 . . 1 0.47 257 19.98 YRDC chr1:38270064 ...... I/T N:120//239 Q:739 ..... 10.523919.98 YTHDF1 chr20:61834581 ...... I/M N:400//822 Q:2297 .... 10.49 822 19.91

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ZBED4 chr22:50277494 . G/S N:77//141 Q:545 ...... 10.55 141 17.32 ZBED4 chr22:50278584 ...... A/V N:115//226 Q:663 . . 1 0.51 226 17.32 ZCCHC11 chr1:52981654 . . . I/T;I/T N:89//168 Q:646 ...... 10.53 168 14.32 ZDHHC4 chr7:6623017 ...... C/R;C/R;C/R;C/R N:90//18. . 1 0.49 183 15.87 ZDHHC5 chr11:57466491 ...... P/L N:69//144 Q:419 ..... 10.48 144 13.89 ZFP36 chr19:39898882 . P/Q N:691//1351 Q:3070 ...... 10.51 1351 90.65 ZFP36L2 chr2:43451957 ...... A/V N:567//1007 Q:2727 . . 1 0.56 1007 123.97 ZFP36L2 chr2:43451976 . . . A/T N:227//528 Q:826 ...... 10.43 528 123.97 ZFYVE27 chr10:99510190 ...... G/D;G/D;G/D;G/D;G/D;G/ . . . 1 0.49 244 13.73 ZNF131 chr5:43161920 . E/V N:68//147 Q:414 ...... 10.46 147 13.44 ZNF259 chr11:116658654 ....P/L N:105//201 Q:457 ...... 10.52 201 22.10 ZNF335 chr20:44592227 ...... R/H N:105//232 Q:506 . 1 0.45 232 12.92 ZNF394 chr7:99091624 ...... Q/R N:455//876 Q:2786 . 1 0.52 876 20.98 ZNF512B chr20:62594771 . E/V N:70//150 Q:434 ...... 10.47 150 14.83 ZNF639 chr3:179051810 ...... N/S N:219//455 Q:1373 . . . 1 0.48 455 12.69 ZNF655 chr7:99159522 . P/A;P/A N:204//205 Q:242 ...... 1120516.33 ZNF787 chr19:56599780 ...... A/V N:26//60 Q:161 ..... 10.43 60 18.42 #L/M N:123//251 Q:721 : "L/M" refers to substitution, to methionine in this case; "N:values//values" refers to number of independent sequences for mutant amino acid over total number of sequences for this position and "Q" refers to quality score of mapped sequence according to CASAVA software (supplied with HiSeq 2000). "*" Represents a stop codon."nI" represents the number of inserted nucleotides.

19 Simon et al.

Supplementary Table 6. List of altered genes in T‐ALL for DAVID analysis Abbreviation Name ABCA7 ATP-binding cassette, sub-family A (ABC1), member 7 ABCB10 ATP-binding cassette, sub-family B (MDR/TAP), member 10 ABCC1 ATP-binding cassette, sub-family C (CFTR/MRP), member 1 ABCD4 ATP-binding cassette, sub-family D (ALD), member 4 ABI1 abl-interactor 1 ABR active BCR-related gene ACAA2 hypothetical LOC648603; acetyl-Coenzyme A acyltransferase 2 ACAP3 ArfGAP with coiled-coil, ankyrin repeat and PH domains 3 ACSF3 acyl-CoA synthetase family member 3 ADAR , RNA-specific ADCK2 aarF domain containing kinase 2 AGPAT2 1-acylglycerol-3-phosphate O-acyltransferase 2 (lysophosphatidic acid acyltransferase, beta) AHNAK AHNAK nucleoprotein AKAP8 A kinase (PRKA) anchor protein 8 AKNA AT-hook ALKBH5 alkB, alkylation repair homolog 5 (E. coli) AMZ2 archaelysin family metallopeptidase 2 ANAPC1 anaphase promoting complex subunit 1; similar to anaphase promoting complex subunit 1 ANAPC7 anaphase promoting complex subunit 7 ANKLE2 ankyrin repeat and LEM domain containing 2 ANKRD11 ankyrin repeat domain 11; hypothetical protein LOC100128265 ANKRD27 ankyrin repeat domain 27 (VPS9 domain) APPL1 adaptor protein, phosphotyrosine interaction, PH domain and containing 1 APRT adenine phosphoribosyltransferase ARGLU1 and glutamate rich 1 ARHGAP30 Rho GTPase activating protein 30 ARHGAP9 Rho GTPase activating protein 9 ARHGEF18 Rho/Rac guanine nucleotide exchange factor (GEF) 18 ARID1A AT rich interactive domain 1A (SWI-like) ARL6IP5 ADP-ribosylation-like factor 6 interacting protein 5 ARPC3 complex, subunit 3, 21kDa ARRDC1 arrestin domain containing 1 ASAH1 N-acylsphingosine (acid ) 1 ASNSD1 asparagine synthetase domain containing 1 ATAD3A ATPase family, AAA domain containing 3A ATF4 activating transcription factor 4 (tax-responsive enhancer element B67); activating transcription factor 4C ATG4B ATG4 autophagy related 4 homolog B (S. cerevisiae) ATG4D ATG4 autophagy related 4 homolog D (S. cerevisiae) ATHL1 ATH1, acid trehalase-like 1 (yeast) ATP2B4 ATPase, Ca++ transporting, plasma membrane 4 ATP6AP2 ATPase, H+ transporting, lysosomal accessory protein 2 AZIN1 antizyme inhibitor 1 B4GALT3 UDP-Gal:betaGlcNAc beta 1,4- , polypeptide 3 BAX BCL2-associated X protein BAZ2A bromodomain adjacent to domain, 2A BCL2L12 BCL2-like 12 ( rich) BIN2 bridging integrator 2 BPTF bromodomain PHD finger transcription factor BRD4 bromodomain containing 4 BRD9 bromodomain containing 9 BRE brain and reproductive organ-expressed (TNFRSF1A modulator)

20 Simon et al.

BSCL2 Bernardinelli-Seip congenital lipodystrophy 2 (seipin) BTBD2 BTB (POZ) domain containing 2 BUD13 BUD13 homolog (S. cerevisiae) BZW2 basic leucine zipper and W2 domains 2 C10orf54 chromosome 10 54 C12orf41 open reading frame 41 C12orf57 chromosome 12 open reading frame 57 C13orf23 chromosome 13 open reading frame 23 C14orf135 chromosome 14 open reading frame 135 C14orf159 chromosome 14 open reading frame 159 C14orf21 chromosome 14 open reading frame 21 C17orf56 open reading frame 56 C17orf70 chromosome 17 open reading frame 70 C17orf85 chromosome 17 open reading frame 85 C17orf95 chromosome 17 open reading frame 95 C1orf35 open reading frame 35 C1orf59 chromosome 1 open reading frame 59 C1orf63 chromosome 1 open reading frame 63 C20orf4 open reading frame 4 C2orf24 open reading frame 24 C2orf29 chromosome 2 open reading frame 29 C3orf63 open reading frame 63 C4orf14 open reading frame 14 C7orf30 chromosome 7 open reading frame 30 C8orf33 chromosome 8 open reading frame 33 C9orf86 chromosome 9 open reading frame 86 CABIN1 binding protein 1 CAMK2G calcium/calmodulin-dependent protein kinase II gamma CANT1 calcium activated 1 CAPN10 calpain 10 CARS cysteinyl-tRNA synthetase CASC3 cancer susceptibility candidate 3 CCDC88B coiled-coil domain containing 88B CCDC88C coiled-coil domain containing 88C CCDC90A coiled-coil domain containing 90A CCNB1 cyclin B1 CCT2 chaperonin containing TCP1, subunit 2 (beta) CCT5 chaperonin containing TCP1, subunit 5 (epsilon) CD38 CD38 molecule CDC25B cell division cycle 25 homolog B (S. pombe) CDC45 CDC45 cell division cycle 45-like (S. cerevisiae) CDCA7L cell division cycle associated 7-like CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) CDT1 chromatin licensing and DNA replication factor 1 CEBPZ CCAAT/enhancer binding protein (C/EBP), zeta CEP110 centrosomal protein 110kDa CERK ceramide kinase CHAF1A chromatin assembly factor 1, subunit A (p150) CHD1L chromodomain DNA binding protein 1-like CHD4 chromodomain helicase DNA binding protein 4 CHD8 chromodomain helicase DNA binding protein 8

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CHMP1A chromatin modifying protein 1A CHPF2 chondroitin sulfate glucuronyltransferase CLASP1 cytoplasmic linker associated protein 1 CLK3 CDC-like kinase 3 CLSTN3 calsyntenin 3 CLTB clathrin, chain (Lcb) CMTM6 CKLF-like MARVEL transmembrane domain containing 6 CNDP2 CNDP dipeptidase 2 (metallopeptidase M20 family) COG1 component of oligomeric golgi complex 1 COQ4 coenzyme Q4 homolog (S. cerevisiae) COQ9 coenzyme Q9 homolog (S. cerevisiae) COTL1 coactosin-like 1 (Dictyostelium) CPXM1 carboxypeptidase X (M14 family), member 1 CRELD2 cysteine-rich with EGF-like domains 2 CSK c-src kinase CTDSP1 CTD (carboxy-terminal domain, RNA II, polypeptide A) small 1 CTR9 Ctr9, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae) CUL9 cullin 9 CUX1 cut-like 1 CWC25 coiled-coil domain containing 49 CYB5B cytochrome b5 type B (outer mitochondrial membrane) CYC1 -1 CYTIP cytohesin 1 interacting protein DCAF13 WD repeats and SOF1 domain containing DCI dodecenoyl-Coenzyme A delta isomerase (3,2 trans-enoyl-Coenzyme A isomerase) DCTN3 dynactin 3 (p22) DDB2 damage-specific DNA binding protein 2, 48kDa DDOST dolichyl-diphosphooligosaccharide-protein DDRGK1 DDRGK domain containing 1 DDX21 DEAD (Asp-Glu-Ala-Asp) box polypeptide 21 DDX49 DEAD (Asp-Glu-Ala-Asp) box polypeptide 49 DDX54 DEAD (Asp-Glu-Ala-Asp) box polypeptide 54 DDX55 DEAD (Asp-Glu-Ala-Asp) box polypeptide 55 DENND3 DENN/MADD domain containing 3 DENND5A DENN/MADD domain containing 5A DGCR6L DiGeorge syndrome critical region gene 6-like DGKA diacylglycerol kinase, alpha 80kDa DHPS deoxyhypusine synthase DHX15 DEAH (Asp-Glu-Ala-His) box polypeptide 15 DHX37 DEAH (Asp-Glu-Ala-His) box polypeptide 37 DHX38 DEAH (Asp-Glu-Ala-His) box polypeptide 38 DIAPH1 diaphanous homolog 1 (Drosophila) DIP2A DIP2 disco-interacting protein 2 homolog A (Drosophila) DNAJA2 DnaJ (Hsp40) homolog, subfamily A, member 2 DNAJB12 DnaJ (Hsp40) homolog, subfamily B, member 12 DNM2 dynamin 2 DNMT1 DNA (cytosine-5-)-methyltransferase 1 DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha DOCK8 dedicator of cytokinesis 8 DPF2 D4, zinc and double PHD fingers family 2 DYM dymeclin DYNC1H1 dynein, cytoplasmic 1, heavy chain 1 DYNC1LI1 dynein, cytoplasmic 1, light intermediate chain 1

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EFTUD2 elongation factor Tu GTP binding domain containing 2 EHBP1L1 EH domain binding protein 1-like 1 EIF2A eukaryotic translation initiation factor 2A, 65kDa EIF2AK4 eukaryotic translation initiation factor 2 alpha kinase 4 EIF3B eukaryotic translation initiation factor 3, subunit B ELAC2 elaC homolog 2 (E. coli) ENTPD6 ectonucleoside triphosphate diphosphohydrolase 6 (putative function) EP300 E1A binding protein p300 EPS15 epidermal growth factor receptor pathway substrate 15 ERAP1 aminopeptidase 1 ERP29 endoplasmic reticulum protein 29 ERV3 endogenous retroviral sequence 3 (includes zinc finger protein H-plk/HPF9) ETV6 ets variant gene 6 (TEL oncogene) EVI2A ecotropic viral integration site 2A EXOC4 exocyst complex component 4 EXOSC6 exosome component 6 FAM113A family with sequence similarity 113, member A FAM134A family with sequence similarity 134, member A FAM134C family with sequence similarity 134, member C FAM160B2 family with sequence similarity 160, member B2 FAM38A family with sequence similarity 38, member A FAM40A family with sequence similarity 40, member A FANCG Fanconi anemia, complementation group G FBXL6 F-box and leucine-rich repeat protein 6 FBXO7 F-box protein 7 FBXW5 F-box and WD repeat domain containing 5 FCGRT Fc fragment of IgG, receptor, transporter, alpha FDFT1 farnesyl-diphosphate farnesyltransferase 1 FHOD1 formin 2 domain containing 1 FKBP4 FK506 binding protein 4, 59kDa FLNA filamin A, alpha ( binding protein 280) FOXM1 forkhead box M1 FPGS folylpolyglutamate synthase FTH1 heavy polypeptide-like 3 pseudogene FYTTD1 forty-two-three domain containing 1 GAK cyclin G associated kinase GAR1 GAR1 ribonucleoprotein homolog (yeast) GARS glycyl-tRNA synthetase GBAS glioblastoma amplified sequence GIT1 G protein-coupled receptor kinase interacting ArfGAP 1 GIT2 G protein-coupled receptor kinase interacting ArfGAP 2 GLTSCR2 pseudogene GNL1 guanine nucleotide binding protein-like 1 GNPAT glyceronephosphate O-acyltransferase GPATCH8 G patch domain containing 8 GRAMD1A GRAM domain containing 1A GTF3A general transcription factor IIIA GTF3C1 general transcription factor IIIC, polypeptide 1, alpha 220kDa HAUS1 HAUS augmin-like complex, subunit 1 HAUS5 HAUS augmin-like complex, subunit 5 HDAC10 10 HDLBP high density lipoprotein binding protein HECTD1 HECT domain containing 1

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Simon et al.

HEXDC hexosaminidase (glycosyl family 20, catalytic domain) containing HIST1H2AC histone cluster 1, H2ac HLA-A major histocompatibility complex, class I, A HLA-DRA major histocompatibility complex, class II, DR alpha HM13 histocompatibility (minor) 13 HMGXB3 HMG box domain containing 3 HSD17B4 hydroxysteroid (17-beta) dehydrogenase 4 HSF1 heat shock transcription factor 1 HSP90B1 heat shock protein 90kDa beta (Grp94), member 1 IARS2 isoleucyl-tRNA synthetase 2, mitochondrial ICMT isoprenylcysteine carboxyl methyltransferase IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial IDH3B isocitrate dehydrogenase 3 (NAD+) beta IDUA iduronidase, alpha-L- IFFO1 intermediate filament family orphan 1 IFI16 interferon, gamma-inducible protein 16 IFNAR2 interferon (alpha, beta and omega) receptor 2 IFNGR2 interferon gamma receptor 2 (interferon gamma transducer 1) IGSF8 immunoglobulin superfamily, member 8 IKZF1 IKAROS family zinc finger 1 (Ikaros) INF2 inverted formin, FH2 and WH2 domain containing INTS1 integrator complex subunit 1 IRF2BP2 interferon regulatory factor 2 binding protein 2 ITM2C integral membrane protein 2C ITPR2 inositol 1,4,5-triphosphate receptor, type 2 ITSN2 intersectin 2 IWS1 IWS1 homolog (S. cerevisiae) JAK3 Janus kinase 3 JARID2 jumonji, AT rich interactive domain 2 JMJD1C jumonji domain containing 1C KATNB1 katanin p80 (WD repeat containing) subunit B 1 KCTD13 potassium channel tetramerisation domain containing 13 KDM3B lysine (K)-specific demethylase 3B KDM6B lysine (K)-specific demethylase 6B KEAP1 kelch-like ECH-associated protein 1 KIAA0182 KIAA0182 KIAA0319L KIAA0319-like KIAA0430 KIAA0430 KIAA1147 KIAA1147 KIAA2013 KIAA2013; hypothetical LOC728138 KIDINS220 kinase D-interacting substrate, 220kDa KIF22 kinesin family member 22 KRI1 KRI1 homolog (S. cerevisiae) LANCL1 LanC lantibiotic synthetase component C-like 1 (bacterial) LAP3 leucine aminopeptidase 3 LARP4B La ribonucleoprotein domain family, member 4B LARP7 La ribonucleoprotein domain family, member 7 LARS leucyl-tRNA synthetase LCP2 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) LENG8 leukocyte receptor cluster (LRC) member 8 LIG1 ligase I, DNA, ATP-dependent LPCAT3 lysophosphatidylcholine acyltransferase 3 LRCH4 leucine-rich repeats and calponin homology (CH) domain containing 4

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Simon et al.

LRDD leucine-rich repeats and death domain containing LRPAP1 low density lipoprotein receptor-related protein associated protein 1 LRWD1 leucine-rich repeats and WD repeat domain containing 1 LSG1 large subunit GTPase 1 homolog (S. cerevisiae) LTA4H leukotriene A4 hydrolase LTV1 similar to putative protein STRF7; LTV1 homolog (S. cerevisiae) MACF1 microtubule-actin crosslinking factor 1 MAGEF1 melanoma antigen family F, 1 MAN2A2 mannosidase, alpha, class 2A, member 2 MAN2B2 mannosidase, alpha, class 2B, member 2 MAP1LC3B microtubule-associated protein 1 light chain 3 beta MAP2K2 mitogen-activated protein kinase kinase 2 pseudogene; mitogen-activated protein kinase kinase 2 MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2 Mar7 membrane-associated ring finger (C3HC4) 7 MBOAT7 membrane bound O-acyltransferase domain containing 7 MBTPS1 membrane-bound transcription factor peptidase, site 1 MCM3AP minichromosome maintenance complex component 3 associated protein MDC1 mediator of DNA-damage checkpoint 1 MED13L mediator complex subunit 13-like MED16 mediator complex subunit 16 MED25 mediator complex subunit 25 MEN1 multiple endocrine neoplasia I MFN2 mitofusin 2 MGRN1 mahogunin, ring finger 1 MGST2 microsomal glutathione S- 2 MIB2 mindbomb homolog 2 (Drosophila) MICAL1 microtubule associated monoxygenase, calponin and LIM domain containing 1 MKI67IP MKI67 (FHA domain) interacting nucleolar phosphoprotein MKNK1 MAP kinase interacting / kinase 1 MKNK2 MAP kinase interacting serine/threonine kinase 2 MKRN1 makorin ring finger protein pseudogene 6; makorin ring finger protein 1 MLF2 myeloid leukemia factor 2 MLH1 mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) MLL myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila) MLL2 myeloid/lymphoid or mixed-lineage leukemia 2 MLL4 myeloid/lymphoid or mixed-lineage leukemia 4 MLLT10 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10 MOBKL2A MOB1, Mps One Binder kinase activator-like 2A (yeast) MPST mercaptopyruvate sulfurtransferase MRPL15 mitochondrial ribosomal protein L15 MRPS23 mitochondrial ribosomal protein S23 MRPS31 mitochondrial ribosomal protein S31 MTDH metadherin MTG1 mitochondrial GTPase 1 homolog (S. cerevisiae) MTMR14 myotubularin related protein 14 MUM1 melanoma associated antigen (mutated) 1 MUTYH mutY homolog (E. coli) MX2 myxovirus (influenza virus) resistance 2 (mouse) MYCBP2 MYC binding protein 2 MYH9 myosin, heavy chain 9, non-muscle MYST1 MYST histone acetyltransferase 1 NAA15 NMDA receptor regulated 1 NACA nascent polypeptide-associated complex alpha subunit

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NADSYN1 NAD synthetase 1 NAGK N-acetylglucosamine kinase NAT10 N-acetyltransferase 10 (GCN5-related) NAT9 N-acetyltransferase 9 (GCN5-related, putative) NBEAL2 neurobeachin-like 2 NBR1 neighbor of BRCA1 gene 1 NCK1 NCK adaptor protein 1 NCOR2 co-repressor 2 NDST2 N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 2 NFIL3 nuclear factor, interleukin 3 regulated NFKB1 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 NFU1 NFU1 iron-sulfur cluster scaffold homolog (S. cerevisiae) NGDN neuroguidin, EIF4E binding protein NHP2 NHP2 ribonucleoprotein homolog (yeast) NIPBL Nipped-B homolog (Drosophila) NISCH nischarin NMRAL1 NmrA-like family domain containing 1 NOP58 NOP58 ribonucleoprotein homolog (yeast) NOTCH1 Notch homolog 1, translocation-associated (Drosophila) NPLOC4 localization 4 homolog (S. cerevisiae) NQO2 NAD(P)H dehydrogenase, quinone 2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog NSD1 nuclear receptor binding SET domain protein 1 NSFL1C NSFL1 (p97) cofactor (p47) NUB1 negative regulator of -like proteins 1 NUDT3 nudix (nucleoside diphosphate linked moiety X)-type motif 3 NUP210 210kDa OGFR opioid growth factor receptor P4HTM prolyl 4-hydroxylase, transmembrane (endoplasmic reticulum) PAICS phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase PARP10 poly (ADP-) polymerase family, member 10 PBXIP1 pre-B-cell leukemia homeobox interacting protein 1 PCM1 pericentriolar material 1 PCMT1 protein-L-isoaspartate (D-aspartate) O-methyltransferase PCNT pericentrin PCNX pecanex homolog (Drosophila) PCNXL3 pecanex-like 3 (Drosophila) PDCD11 programmed cell death 11 PDIA4 protein disulfide isomerase family A, member 4 PDIA6 protein disulfide isomerase family A, member 6 PDRG1 and DNA-damage regulated 1 PEPD peptidase D PEX6 peroxisomal biogenesis factor 6 PFKL phosphofructokinase, liver PGM1 phosphoglucomutase 1 PGS1 phosphatidylglycerophosphate synthase 1 PHIP pleckstrin homology domain interacting protein PHKB kinase, beta PHRF1 PHD and ring finger domains 1 PI4KB phosphatidylinositol 4-kinase, catalytic, beta PIGT phosphatidylinositol glycan anchor biosynthesis, class T PIK3IP1 phosphoinositide-3-kinase interacting protein 1 PIK3R2 phosphoinositide-3-kinase, regulatory subunit 2 (beta)

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PIKFYVE phosphoinositide kinase, FYVE finger containing PITPNM1 phosphatidylinositol transfer protein, membrane-associated 1 PITRM1 pitrilysin metallopeptidase 1 PKN1 protein kinase N1 PLEC protein 500kDa PLXND1 plexin D1 PMPCA peptidase (mitochondrial processing) alpha PNN pinin, desmosome associated protein PNRC1 proline-rich nuclear receptor coactivator 1 POLE polymerase (DNA directed), epsilon POLR3E polymerase (RNA) III (DNA directed) polypeptide E (80kD) POLRMT polymerase (RNA) mitochondrial (DNA directed) PPHLN1 periphilin 1 PPIL2 peptidylprolyl isomerase (cyclophilin)-like 2 PPP1R15B 1, regulatory (inhibitor) subunit 15B PPP4C protein phosphatase 4 (formerly X), catalytic subunit PRDX6 peroxiredoxin 6 PRKCSH protein kinase C substrate 80K-H PRNP prion protein PSD4 pleckstrin and Sec7 domain containing 4 PSMD9 proteasome (prosome, macropain) 26S subunit, non-ATPase, 9 PSMF1 proteasome (prosome, macropain) inhibitor subunit 1 (PI31) PTEN phosphatase and tensin homolog; phosphatase and tensin homolog pseudogene 1 PTPN23 protein tyrosine phosphatase, non-receptor type 23 QRICH1 glutamine-rich 1 R3HDM2 R3H domain containing 2 RAB4B RAB4B, member RAS oncogene family RABGGTA Rab geranylgeranyltransferase, alpha subunit RALY RNA binding protein, autoantigenic (hnRNP-associated with lethal yellow homolog (mouse)) RANBP2 RAN binding protein 2 RAP1GDS1 RAP1, GTP-GDP dissociation stimulator 1 RASAL3 RAS protein activator like 3 RBM15 RNA binding motif protein 15 RBM19 RNA binding motif protein 19 RBM5 RNA binding motif protein 5 RBM6 RNA binding motif protein 6 RCC2 regulator of chromosome condensation 2 REXO1 REX1, RNA 1 homolog (S. cerevisiae) RFWD2 ring finger and WD repeat domain 2 RHOG ras homolog gene family, member G (rho G) RIN3 Ras and Rab interactor 3 RLTPR RGD motif, leucine rich repeats, tropomodulin domain and proline-rich containing RNASEH1 H1 RNF113A ring finger protein 113A RNF126 ring finger protein 126 RNF213 ring finger protein 213 RNF40 ring finger protein 40 RNF44 ring finger protein 44 RNH1 ribonuclease/ inhibitor 1 RNPC3 RNA-binding region (RNP1, RRM) containing 3 ribosomal protein L10; ribosomal protein L10 pseudogene 15; ribosomal protein L10 pseudogene 6; ribosomal RPL10 protein L10 pseudogene 16; ribosomal protein L10 pseudogene 9 RPL31 ribosomal protein L31 pseudogene 49; ribosomal protein L31 pseudogene 17; ribosomal protein L31

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ribosomal protein L7-like 1; ribosomal protein L7 pseudogene 14; ribosomal protein L7 pseudogene 21; RPL7L1 ribosomal protein L7 pseudogene 22; ribosomal protein L7 pseudogene 46 RPN1 ribophorin I RPS15 ribosomal protein S15 pseudogene 5; ribosomal protein S15 RPUSD3 RNA pseudouridylate synthase domain containing 3 RRM1 ribonucleotide reductase M1 RRP1 ribosomal RNA processing 1 homolog (S. cerevisiae) S100A9 S100 calcium binding protein A9 SAMD1 sterile alpha motif domain containing 1 SART1 squamous cell carcinoma antigen recognized by T cells SATB1 SATB homeobox 1 SBF1 SET binding factor 1; SET binding factor 1 pseudogene 1 SCNM1 sodium channel modifier 1 SCRIB scribbled homolog (Drosophila) SCRN2 secernin 2 SDCCAG3 serologically defined colon cancer antigen 3; similar to Serologically defined colon cancer antigen 3 SDF4 stromal cell derived factor 4 SDR39U1 short chain dehydrogenase/reductase family 39U, member 1 SEC23B Sec23 homolog B (S. cerevisiae) SEC24B SEC24 family, member B (S. cerevisiae) SEC31B SEC31 homolog B (S. cerevisiae) SELPLG P ligand Sep9 septin 9 SERBP1 SERPINE1 mRNA binding protein 1 SETDB1 SET domain, bifurcated 1 SETX senataxin SF1 splicing factor 1 SFI1 Sfi1 homolog, spindle assembly associated (yeast) SFRS15 splicing factor, arginine/serine-rich 15 SH2B1 SH2B adaptor protein 1 SH2D3C SH2 domain containing 3C SH3TC1 SH3 domain and tetratricopeptide repeats 1 SKIV2L superkiller viralicidic activity 2-like (S. cerevisiae) SLC12A9 solute carrier family 12 (potassium/chloride transporters), member 9 SLC25A46 solute carrier family 25, member 46 SLC35E1 solute carrier family 35, member E1 SLC39A6 solute carrier family 39 (zinc transporter), member 6 SLC4A2 solute carrier family 4, anion exchanger, member 2 (erythrocyte membrane protein band 3-like 1) SLK STE20-like kinase (yeast) SMCR8 Smith-Magenis syndrome chromosome region, candidate 8 SMG1 SMG1 homolog, phosphatidylinositol 3-kinase-related kinase (C. elegans) SMG5 Smg-5 homolog, nonsense mediated mRNA decay factor (C. elegans) SNAP47 synaptosomal-associated protein, 47kDa SON SON DNA binding protein SORL1 sortilin-related receptor, L(DLR class) A repeats-containing SPAG5 sperm associated antigen 5 SPEN spen homolog, transcriptional regulator (Drosophila) SPG11 spastic paraplegia 11 (autosomal recessive) SPN sialophorin SPNS1 spinster homolog 1 (Drosophila) SPNS3 spinster homolog 3 (Drosophila) SPRY2 sprouty homolog 2 (Drosophila) SRCAP Snf2-related CREBBP activator protein

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STAT5B signal transducer and activator of transcription 5B STK11IP serine/threonine kinase 11 interacting protein STK38 serine/threonine kinase 38 STT3B STT3, subunit of the oligosaccharyltransferase complex, homolog B (S. cerevisiae) SUZ12 suppressor of zeste 12 homolog (Drosophila) SYMPK symplekin TALDO1 transaldolase 1 TAP2 transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) TARS threonyl-tRNA synthetase TAX1BP3 Tax1 (human T-cell leukemia virus type I) binding protein 3 TBL3 transducin (beta)-like 3 TCF12 transcription factor 12 TCF3 transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47) TELO2 TEL2, maintenance 2, homolog (S. cerevisiae) TIMM44 translocase of inner mitochondrial membrane 44 homolog (yeast) TJAP1 tight junction associated protein 1 (peripheral) TKT transketolase TLK1 tousled-like kinase 1 TM9SF3 transmembrane 9 superfamily member 3 TMC6 transmembrane channel-like 6 TMEM131 transmembrane protein 131 TNFAIP3 tumor necrosis factor, alpha-induced protein 3 TNPO3 transportin 3 TNRC18 trinucleotide repeat containing 18 TP53 tumor protein p53 TPRA1 G protein-coupled receptor 175 TRAF3IP3 TRAF3 interacting protein 3 TRAP1 TNF receptor-associated protein 1 TRIM22 tripartite motif-containing 22 TRIM56 tripartite motif-containing 56 TRMT2A TRM2 tRNA methyltransferase 2 homolog A (S. cerevisiae) TSEN54 tRNA splicing 54 homolog (S. cerevisiae) TSPYL4 TSPY-like 4 TSSC4 tumor suppressing subtransferable candidate 4 TTC19 tetratricopeptide repeat domain 19 TTC37 tetratricopeptide repeat domain 37 TTC38 tetratricopeptide repeat domain 38 TUBGCP2 tubulin, gamma complex associated protein 2 TUBGCP6 tubulin, gamma complex associated protein 6 TXNDC11 thioredoxin domain containing 11 U2AF1L4 U2 small nuclear RNA auxiliary factor 1-like 4 UBAP1 ubiquitin associated protein 1 UBAP2L ubiquitin associated protein 2-like UBE2M ubiquitin-conjugating E2M (UBC12 homolog, yeast); ubiquitin-conjugating enzyme E2M pseudogene 1 UBE2O ubiquitin-conjugating enzyme E2O UBE2Q1 ubiquitin-conjugating enzyme E2Q family member 1 UBE3A ubiquitin protein ligase E3A UBE4B ubiquitination factor E4B (UFD2 homolog, yeast) UBQLN1 ubiquilin 1 UBQLN2 ubiquilin 2 UBR4 ubiquitin protein ligase E3 component n-recognin 4 UGGT1 UDP-glucose ceramide -like 1 ULK1 unc-51-like kinase 1 (C. elegans)

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UNC13D unc-13 homolog D (C. elegans) UNC45A unc-45 homolog A (C. elegans) UQCRFS1 Rieske iron-sulfur polypeptide 1 USP19 ubiquitin specific peptidase 19 USP3 ubiquitin specific peptidase 3 USP34 ubiquitin specific peptidase 34 USP36 ubiquitin specific peptidase 36 USP4 ubiquitin specific peptidase 4 (proto-oncogene) USP48 ubiquitin specific peptidase 48 UTP18 UTP18, small subunit (SSU) processome component, homolog (yeast) VAT1 vesicle amine transport protein 1 homolog (T. californica) VAV3 vav 3 guanine nucleotide exchange factor VPS39 vacuolar protein sorting 39 homolog (S. cerevisiae) VPS45 vacuolar protein sorting 45 homolog (S. cerevisiae) VRK3 vaccinia related kinase 3 WBP11 WW domain binding protein 11 WDR46 WD repeat domain 46 WDR48 WD repeat domain 48 WDR85 WD repeat domain 85 WIZ widely interspaced zinc finger motifs XPC xeroderma pigmentosum, complementation group C XPO5 exportin 5 XYLT1 I YRDC yrdC domain containing (E. coli) YTHDF1 YTH domain family, member 1 ZBED4 zinc finger, BED-type containing 4 ZCCHC11 zinc finger, CCHC domain containing 11 ZDHHC4 zinc finger, DHHC-type containing 4 ZDHHC5 zinc finger, DHHC-type containing 5 ZFP36 zinc finger protein 36, C3H type, homolog (mouse) ZFP36L2 zinc finger protein 36, C3H type-like 2 ZFYVE27 zinc finger, FYVE domain containing 27 ZNF131 zinc finger protein 131 ZNF259 zinc finger protein 259 ZNF335 zinc finger protein 335 ZNF394 zinc finger protein 394 ZNF512B zinc finger protein 512B ZNF639 zinc finger protein 639 ZNF655 zinc finger protein 655 ZNF787 zinc finger protein 787 30 Simon et al.

Supplementary Table 7. Functional annotation of genetic anomalies observed in human adult T-ALL

Fold Categories Count % P Value Pop Hits Enrichment Benjamini chromatin regulator 24 0,41 7,7E-08 213 3,84 5,0E-06 ubl conjugation pathway 36 0,61 2,9E-06 509 2,41 1,4E-04 RNA-binding 35 0,60 2,6E-05 540 2,21 9,0E-04 ligase 24 0,41 3,5E-05 305 2,68 1,1E-03 endoplasmic reticulum 41 0,70 6,9E-05 713 1,96 2,0E-03 30 0,51 1,0E-04 461 2,22 2,6E-03 rRNA processing 9 0,15 3,9E-04 61 5,03 9,3E-03 helicase 13 0,22 5,8E-04 134 3,31 1,2E-02 ubl conjugation 33 0,56 6,1E-04 588 1,91 1,2E-02 tpr repeat 14 0,24 8,8E-04 160 2,98 1,7E-02 bromodomain 7 0,12 8,8E-04 39 6,12 1,6E-02 ATP 17 0,29 1,6E-03 236 2,46 2,7E-02 DNA damage 15 0,26 2,9E-03 205 2,50 4,1E-02 wd repeat 18 0,31 3,3E-03 276 2,22 4,4E-02 DNA repair 14 0,24 4,2E-03 191 2,50 5,5E-02 repressor 24 0,41 4,8E-03 435 1,88 6,1E-02 SH2 domain 10 0,17 5,3E-03 111 3,07 6,4E-02 transit peptide 25 0,43 7,1E-03 476 1,79 8,2E-02 cytoskeleton 31 0,53 7,4E-03 636 1,66 8,4E-02 chromosomal rearrangement 17 0,29 8,3E-03 279 2,08 9,0E-02 microtubule 15 0,26 8,3E-03 231 2,21 8,8E-02 mRNA processing 16 0,27 9,9E-03 260 2,10 1,0E-01

Mutated alleles in the functional categories can be retrieved by submitting supplementary Table 6 to DAVID. Count: number of genes with anomalies in patients listed in Supplementary Table 2; %: proportion of altered genes (count) among the group of 564 genetic anomalies selected as the protocol shown in Figure 3A; Pop Hits: total number of genes in the annotated per category. A total of 19235 genes were considered by DAVID. Categories representing over 5% of the human genome or about 1000 genes were excluded.

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Supplementary Table 7. List of acquired SNPs tested in normal non leukemic GENES Position Patient Ref Normal Tumoral HiSeq Status ARID1A chr1:27097679 08H028 A A A/G 299/289 Acquired ARID1A chr1:27100171 08H125 C C/T C/T 292/284 Germinal CHD4 chr12:6697097 05H125 G G A/G 563/675 Acquired DNMT1 chr19:10265138 08H125 C C/T C/T 221/242 Germinal DNMT3A chr2:25467436 11H099 A A C/A 214/223 Acquired DNMT3A chr2:25457242 08H028 C C T 668 Acquired EP300 chr22:41569733 05H129 A A/G A/G 190/194 Germinal EP300 chr22:41546030 09H030 C C/G C/G 352/333 Germinal IDH2 chr15:90630398 07H033 C T C/T 839/806 Acquired IDH3B chr20:2639474 07H033 G A/G A/G 203/321 Germinal JARID2 chr6:15520318 03H078 G G A/G 217/258 Acquired KDM6B chr17:7752825 05H080 G G/T G/T 49/88 Germinal KDM6B chr17:7750633 09H030 G A/G A/G 115/106 Germinal TP53 chr17:7577568 09h030 C C A/C 287/213 Acquired TP53 chr17:7578449 03h005 C C C/T 277/321 Acquired TRRAP chr7:98554134 03H078 C C/T C/T 101/33 Germinal HiSeq: number of sequences for each bp indicated in "tumoral" column

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