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Supplemental Table S1. Clinico-Molecular Characteristics of Patients Included in the Training Cohort and Summary of the Obtained Results

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Supplemental Table S1. Clinico-Molecular Characteristics of Patients Included in the Training Cohort and Summary of the Obtained Results Supplementary material J Med Genet Supplemental Table S1. Clinico-molecular characteristics of patients included in the training cohort and summary of the obtained results. Abbreviations: preT-LBL: precursor T-cell lymphoblastic lymphoma; T-LBL: T-cell lymphoblastic lymphoma; ALL: acute lymphoblastic leukaemia; sPNET, supratentorial primitive neuroectodermal tumor; B-ALL, B-cell acute lymphoblastic leukaemia; T-NHL, T-cell non-Hodgkin lymphoma; EC, endometrial cancer; CRC: colorectal cancer; NHL: non-Hodgkin lymphoma; OC, ovarian cancer; LC, liver cancer; BC, breast cancer; y, years; m, months; NP, not performed; gMSI, germline microsatellite instability; gMSI detection: -, no detection; +, detection; hs-MSI, high-sensitivity microsatellite instability; hs-MSI detection: -, no detection; +, detection. (*) Samples previously analyzed in Gallon et al., 2019. ( ‡) Another sample from the same patient was previously analyzed in Gallon et al., 2019. gMSI (according to Ingham et al., 2013) hs-MSI score MMR Cancer diagnosis Disease stage at blood Result of clonality Patient ID Family ID affected Germline variant (cDNA) Germline variant (protein) Available sample Age at sampling before blood Tumours (age of onset) gMSI hs-MSI sampling testing D2S123 D17S250 D17S791 186 MS 231 MS gene sampling detection detection CMMRD: Burkitt lymphoma (2y), preT-LBL CMMRD-01 (91‡) Family A MSH6 c.[2653A>T];[2653A>T] p.[Lys885*];[Lys885*] Blood 9y Yes Under chemotherapy Polyclonal -0.01 -0.02 -0.04 - 22.03 16.25 + (3y and 8y) Buccal mucosa 9y Yes Under chemotherapy NP NP NP NP 19.23 14.34 + CMMRD-02 Family A MSH6 c.[2653A>T];[2653A>T] p.[Lys885*];[Lys885*] Blood 6y Yes Under chemotherapy Wilms tumour (5y), T-LBL (8y) NP -0.02 -0.02 -0.02 - 22.73 17.87 + CMMRD-03 (49‡) MLH1 c.[332C>T]; [332C>T] p.[Ala111Val];[Ala111Val] Blood 15m Yes Under chemotherapy T-LBL (7m) Polyclonal 0.09 0.11 -0.03 + 59.22 45.80 + CMMRD-04 (51‡) PMS2 c.[2007-2A>G];[2007-2A>G] Blood 3y Yes Cancer affected ALL (2y), Glioblastoma (3y) NP 0.02 0.17 0.34 + 25.42 19.49 + sPNET (7y), Sigmoidal CMMRD-05 (71*) PMS2 c.[862C>T];[862C>T] p.[Gln288*];[Gln288*] Blood 10y Yes Cancer affected NP 0.03 0.13 0.21 + 23.26 18.34 + adenocarcinoma (10y) Fusion transcript from PMS2 exon 10 CMMRD-06 (A*) PMS2 Complex rearrangement into a sequence derived from intron Blood 5y Yes Cancer affected Glioblastoma (5y) NP 0.11 0.26 0.36 + 35.20 27.50 + 14 of CCZ1B gene CMMRD-07 (43‡) MSH6 c.[467C>G];[1316A>G] p.[Ser156*];[Asp439Gly] Blood 4y Yes Cancer affected Anaoplastic medulloblastoma (4y) NP -0.03 -0.01 -0.03 - 14.84 11.43 + CMMRD-08 (83*) MSH6 c.[1135_1139del];[2277_2293del] p.[Arg379*];[Glu760Profs*6] Blood 8y Yes Healthy B-ALL (3y), T-NHL (7y) NP -0.02 -0.02 -0.02 - 25.70 19.83 + CMMRD-09 (B‡) MSH6 c.[2238dup];[2980T>A] p.[Leu747Serfs*9];[Tyr994Asn] Blood 6y Yes Cancer affected Medulloblastoma (6y) NP -0.01 -0.01 -0.02 - 24.44 18.11 + Lymphoma (18y), Lymphoma (37y), CMMRD-10 PMS2 c.[24-2A>G];[24-2A>G] p.[Ser8Argfs*4];[Ser8Argfs*4] Blood 43y Yes Cancer affected EC (39y), 3 independent CRC (43y), NP 0.05 0.05 0.08 + 17.03 13.52 + Lymphoma (43y) CMMRD-11 MSH6 c.[742C>T];[742C>T] p.[Arg248*];[Arg248*] Blood 1y Yes Cancer affected NHL (1y) Polyclonal 0.02 -0.01 -0.05 - 23.89 18.18 + Lynch syndrome: Lynch-01 MLH1 c.1590_1598dup p.(Gly532_Val534dup) Blood 54y No Healthy No tumor NP NP NP NP NP 0 0 - Lynch-02 MLH1 c.1731G>A p.Ser556Argfs*14 Blood 43y No Healthy No tumor NP NP NP NP NP 2.78 2.49 - Lynch-03 Family B MLH1 c.1865T>A p.Leu622His Blood 43y No Healthy No tumor NP NP NP NP NP 1.11 0.83 - Lynch-04 MLH1 c.1865T>A p.Leu622His Blood 31y No Healthy No tumor NP NP NP NP NP 2.81 2.50 - Lynch-05 Family C MLH1 c.199G>A p.(Gly67Arg) Blood 25y No Healthy No tumor NP NP NP NP NP 0 0 - Lynch-06 MLH1 c.208-?_306+?del p.(?) Blood 40y No Healthy No tumor NP NP NP NP NP 0.56 0.41 - Lynch-07 Family D MLH1 c.350C>T p.(Thr117Met) Blood 35y No Healthy No tumor NP NP NP NP NP 0 0 - Lynch-08 Family D MLH1 c.350C>T p.(Thr117Met) Blood 52y No Healthy No tumor NP NP NP NP NP 0.56 0.41 - Lynch-09 Family E MLH1 c.676C>T p.(Arg226*) Blood 26y No Healthy No tumor NP NP NP NP NP 0.60 0.45 - Lynch-10 MSH2 c.2635-5_2635-3inv p.(?) Blood 33y No Healthy No tumor NP NP NP NP NP 1.66 1.23 - Lynch-11 MSH2 c.1980_1981del p.(Asp660Glufs*15) Blood 41y No Healthy No tumor NP NP NP NP NP 0.55 0.41 - Lynch-12 MSH2 c.2021dup p.(Lys675*) Blood 30y No Healthy No tumor NP NP NP NP NP 3.33 2.48 - Lynch-13 MSH2 c.2222_2223del p.(Lys741Argfs*8) Blood 40y No Healthy No tumor NP NP NP NP NP 0.55 0.41 - Lynch-14 MSH2 c.367-6_370dup p.(Ser124Tyrfs*12) Blood 37y No Healthy No tumor NP NP NP NP NP 0.55 0.41 - Lynch-15 Family F MSH2 c.746_747del p.(Lys249Argfs*6) Blood 36y No Healthy No tumor NP NP NP NP NP 0.56 0.41 - Lynch-16 MSH6 c.1477G>T p.(Glu493*) Blood 37y No Healthy No tumor NP NP NP NP NP 1.17 0.88 - Lynch-17 Family G MSH6 c.1739C>A p.(Ser580*) Blood 65y No Healthy No tumor NP NP NP NP NP 1.10 0.82 - Lynch-18 MSH6 c.2188dup p.(Tyr730Leufs*26) Blood 24y No Healthy No tumor NP NP NP NP NP 1.10 0.82 - Lynch-19 MSH6 c.236C>A p.(Ser79*) Blood 52y No Healthy No tumor NP NP NP NP NP 0.56 0.41 - González-Acosta M, et al. J Med Genet 2019; 0:1–5. doi: 10.1136/jmedgenet-2019-106272 Supplementary material J Med Genet Lynch-20 MSH6 c.3238_3239del p.(Leu1080Valfs*12) Blood 59y No Healthy No tumor NP NP NP NP NP 1.11 0.83 - Lynch-21 MSH6 c.3261del p.(Phe1088Serfs*2) Blood 41y No Healthy No tumor NP NP NP NP NP 1.66 1.64 - Lynch-22 MSH6 c.3261del p.(Phe1088Serfs*2) Blood 53y No Healthy No tumor NP NP NP NP NP 1.68 1.26 - Lynch-23 PMS2 c.1A>G p.(?) Blood 41y No Healthy No tumor NP NP NP NP NP 0 0 - Lynch-24 PMS2 c.538-3C>G p.(Glu180Glnfs*5, Glu180_Gln235del) Blood 38y No Healthy No tumor NP NP NP NP NP 0 0 - Lynch-25 PMS2 c.780del p.(Asp261Metfs*46) Blood 26y No Healthy No tumor NP NP NP NP NP 0 0 - Lynch-26 PMS2 c.989-2A>G p.Glu330_Gly381del Blood 61y No Healthy No tumor NP NP NP NP NP 0.55 0.41 - Lynch-27 MLH1 c.1852_1854del p.(Lys618del) Blood 39y Yes Unknown CRC (38y) NP NP NP NP NP 1.73 1.30 - Lynch-28 MLH1 c.1865T>A p.Leu622His Blood 40y Yes Unknown CRC (39y) NP NP NP NP NP 0.57 0.43 - Lynch-29 Family B MLH1 c.1865T>A p.Leu622His Blood 34y Yes Healthy CRC (33y), EC (39y) NP NP NP NP NP 1.11 0.83 - Lynch-30 Family C MLH1 c.199G>A p.(Gly67Arg) Blood 54y Yes Healthy CRC (39y) NP NP NP NP NP 0 0 - Lynch-31 MLH1 c.306+5G>A p.[Lys70_Glu102del, Glu102Phefs*18] Blood 64y Yes Healthy CRC (50y), CRC (55y) NP NP NP NP NP 1.63 1.21 - Lynch-32 MLH1 c.306+5G>A p.[Lys70_Glu102del, Glu102Phefs*18] Blood 51y Yes Unknown CRC (40y) NP NP NP NP NP 0.56 0.41 - Lynch-33 Family E MLH1 c.676C>T p.(Arg226*) Blood 51y Yes Healthy EC (39y), CRC (39y), CRC (46y) NP NP NP NP NP 2.78 2.07 - Lynch-34 MSH2 c.518T>G p.(Leu173Arg) Blood 44y Yes Healthy OC (43y), CRC (45y) NP NP NP NP NP 2.84 2.53 - Lynch-35 MSH2 c.689_691delinsTT p.(Ala230Valfs*16) Blood 46y Yes Unknown OC (42y) NP NP NP NP NP 1.11 0.83 - Lynch-36 Family F MSH2 c.746_747del p.(Lys249Argfs*6) Blood 30y No Unknown LC (34y) NP NP NP NP NP 0 0 - Lynch-37 MSH2 c.942+3A>T p.(Val265_Gln314del) Blood 41y Yes Unknown EC (40y) NP NP NP NP NP 2.20 1.65 - Lynch-38 MSH2 Deletion E7-E16 p.(?) Blood 53y Yes Unknown BC (51y), EC (51y) NP NP NP NP NP 1.10 1.22 - Lynch-39 MSH2 Duplication E11-E16 p.(?) Blood 64y Yes Healthy CRC (54y) NP NP NP NP NP 1.65 1.23 - Lynch-40 Family G MSH6 c.1739C>A p.(Ser580*) Blood 69y Yes Healthy CRC (69y) NP NP NP NP NP 1.10 0.82 - Lynch-41 MSH6 c.2147_2148del p.(Thr716Serfs*39) Blood 47y Yes Healthy CRC (41y), CRC (52y) NP NP NP NP NP 0 0.41 - Lynch-42 MSH6 c.255dup p.(Thr86Hisfs*4) Blood 44y Yes Unknown CRC (42y) NP NP NP NP NP 0.55 0.4 - Lynch-43 MSH6 c.2731C>T p.(Arg911*) Blood 70y Yes Healthy CRC (68y), PC (73y) NP NP NP NP NP 1.10 0.82 - Lynch-44 MSH6 c.3202C>T p.(Arg1068*) Blood 58y Yes Healthy CRC (50y) NP NP NP NP NP 2.78 2.06 - Lynch-45 PMS2 c.164-2A>G p.(Asp55Alafs*2) Blood 67y Yes Cancer affected CRC (66y) NP NP NP NP NP 1.70 1.70 - Lynch-46 PMS2 c.2444C>T p.(Ser815Leu) Blood 59y Yes Healthy OC (54y) NP NP NP NP NP 0 0.41 - Lynch-47 PMS2 c.903G>T p.(Tyr268*) Blood 68y Yes Healthy CRC (68y), CRC (68y) NP NP NP NP NP 0.55 0.41 - Lynch-48 PMS2 C.943C>T p.(Arg315*) Blood 53y Yes Healthy CRC (49y) NP NP NP NP NP 0 0 - Healthy controls: CONTROL_01 Blood 65y No Healthy No tumor NP NP NP NP NP 2.23 1.79 - CONTROL_02 Blood 52y No Healthy No tumor NP NP NP NP NP 1.66 1.33 - CONTROL_03 Blood 59y No Healthy No tumor NP NP NP NP NP 1.64 1.32 - CONTROL_04 Blood 62y No Healthy No tumor NP NP NP NP NP 1.12 0.9 - CONTROL_05 Blood 52y No Healthy No tumor NP NP NP NP NP 1.09 0.87 - CONTROL_06 Blood 56y No Healthy No tumor NP NP NP NP NP 0.54 0.44 - CONTROL_07 Blood 61y No Healthy No tumor NP NP NP NP NP 1.1 0.88 - CONTROL_08 Blood 56y No Healthy No tumor NP NP NP NP NP 3.89 3.11 - CONTROL_09 Blood 56y No Healthy No tumor NP NP NP NP NP 2.86 2.28 - CONTROL_10 Blood 51y No Healthy No tumor NP NP NP NP NP 1.1 0.88 - CONTROL_11 Blood 52y No Healthy No tumor NP NP NP NP NP 0.55 0.44 - CONTROL_12 Blood 65y No Healthy No tumor NP NP NP NP NP 0 0 - CONTROL_13 Blood 50y No Healthy No tumor NP NP NP NP NP 0 0 - González-Acosta M, et al.
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