Supplementary table 1. Assignment of hyperdiploidy by FISH and clinical parameters of Group 1 patients

FISH Based Trisomy Index MAYO T3 T9 T11 T15 T19 TC class Heavy Chain Light Chain Status 13 VH/CH PCLI GEP Cluster Albumin B2M ISS Stage Bone Disease M003 ND + + + ND D1 G Kappa Relapse 0 0 4.2 1 3.4 4.16 II - M029 ND + - + ND D1 G lambda Relapse 0 0 3 1 2.74 7.29 III Y M037 ND + + - ND D2 G Kappa New 1 0 0.2 2 2.77 6.54 III Y M051 ND + - + ND D2 G Kappa Relapse 1 0 4.8 1 3.24 8.46 III Y M058 ND + + + ND D1 G lambda New 1 0 0 4 3.15 7.18 III N M059 ND + - + ND D1 L Kappa New 0 1 0 4 3.94 2.28 I Y M061 + + - - - D1 L Kappa New 0 0 0 2 2.67 2.61 II Y M082 ND + + - ND D2 A Kappa Relapse 1 0 5.8 1 2.76 - - Y M113 + + - - - D1 G lambda Relapse 0 0 2.2 4 3.79 11.6 III Y M123 ND + - + ND D1+D2 G Kappa Relapse 1 1 1.2 2 4.28 1.7 I Y M128 ND + + + ND D1 L Kappa Relapse 0 1 2.3 4 4.17 7.4 III Y M131 ND - + + ND D1 G Kappa Relapse 0 0 4.4 4 4.88 8.74 III Y M135 ND + + + ND D1 G Kappa New 0 0 0 3 4.01 5.23 II Y M142 ND + + - ND D1 A Kappa New 0 0 0.2 3 3.92 5.23 II Y M163 ND + + + ND D1 A Kappa New 0 0 0.4 3 2.96 2.06 II N M198 ND + + + ND D1 A Kappa New 0 0 0.4 2 3.1 3.3 II Y M200 ND + + - ND D2 A Kappa New 0 0 3.8 1 2.5 3.16 II Y M218 ND + + + ND D1 A lambda New 0 0 0 3 3.6 4.31 II Y M227 ND - + + ND D1 L Kappa New 1 0 0 3 3.9 2.76 I Y M229 ND - + + ND D1 G Kappa Relapse 0 0 3.8 1 4.3 8.77 III Y M230 ND + + - ND D1 A Kappa New 1 1 1 4 3.6 6.94 III Y M235 ND + + + ND D1 G Kappa Relapse 0 0 0.2 2 4 2.37 I Y M245 ND + - + ND D1 G Kappa New 0 0 0 4 3.9 2.11 I Y M249 ND + + + ND D1 A Kappa New 1 0 5.1 1 3 5.32 II Y M254 ND + + + ND D1 G Kappa Relapse 0 0 2.6 4 4 2.01 I Y M264 ND + + + ND D1 G Kappa New 1 0 0.6 2 4 6.55 III N M276 ND + + + ND D1 G Kappa Relapse 0 0 4.7 1 4.1 - - Y M279 + + - - - D1 A Kappa New 0 0 1.2 2 3.9 6.31 III Y M288 ND + - + ND NONE G lambda New 0 0 9.4 1 2.3 1.74 II Y M300 ND + + + ND NONE G Kappa New 1 1 1.2 3 3.8 2.59 I N M304 ND + + + ND D1+D2 G lambda New 0 0 0 2 3.6 3.34 I N M307 ND + + - ND D1+D2 A lambda New 0 0 0 1 3.7 6.22 III Y M315 ND + + + ND D1 G Kappa Relapse 0 1 2.4 4 3.7 3.39 I Y M318 ND + + + ND D1 L lambda New 0 1 4 4 3.8 2.76 I Y M337 + - + - - D1 A Kappa New 1 0 0 2 3.8 5.12 II Y M338 ND + + + ND D1 G Kappa New 0 0 2.8 4 3.3 1.96 II Y M359 ND + + + ND D1 G Kappa New 0 0 0.2 3 3.8 4.35 II Y M370 ND + - + ND D1 G Kappa New 1 0 0 2 4 9.67 III N M373 ND + + + ND D1 G lambda New 0 0 0 4 3.5 1.31 I Y M380 ND + + + ND D1 G Kappa New 0 0 2 3 3.9 2.11 I Y M383 ND + + + ND D1 G Kappa New 0 0 0.2 1 3.3 4.73 II Y M407 ND + + + ND D1 A Kappa New 0 0 0.6 4 4.3 1.65 I Y M410 ND + - + ND NONE A Kappa New 0 0 0 3 3.6 2.14 I Y M412 ND + + - ND D1 G Kappa New 0 0 0.2 3 2.9 3.43 II Y M444 ND + + + ND D1 G Kappa Relapse 0 0 0.4 4 4 5.45 II Y M467 ND + + + ND D1 A lambda New 0 0 0 3 3.9 1.91 I N M490 ND + + + ND D1 G Kappa Relapse 0 1 4 3 3.82 4.45 II Y M687 ND + + + ND D2 L lambda New 1 1 0 3 3.7 2.74 I N M700 ND + + + ND D1 G Kappa New 1 1 0.8 2 3.6 2.4 I Y M789 ND + + + ND D1 G Kappa Relapse 0 0 1 4 5 - - Y M790 ND + + + ND D1 G Kappa New 0 0 0.8 3 2.9 3.97 II Y M806 ND + + + ND D1 G Kappa New 0 0 0 2 2.4 - - N M822 ND + + + ND D1+D2 A lambda New 1 0 2.2 1 3.9 2.25 I N Abbreviation: ND = not done; M = Male; F = Female; L = light chains only; T3, T9. T11. T15. T19 = trisomies of 3,9,11,15 and 19 respectively. Supplementary table 2. lists used for each recursive clustering.

1st Recursive Clustering 2nd Recursive Clustering 3rd Recursive Clustering 4th Recursive Clustering Probe ID Name Probe ID Gene Name Probe ID Gene Name Probe ID Gene Name 200602_at APP 200602_at APP 200602_at APP 200602_at APP 200799_at 200799_at 200799_at 200799_at 200951_s_at CCND2 200951_s_at CCND2 200951_s_at CCND2 200953_s_at CCND2 200953_s_at CCND2 200953_s_at CCND2 201005_at CD9 201005_at CD9 201005_at CD9 201005_at CD9 201105_at LGALS1 201105_at LGALS1 201105_at LGALS1 201105_at LGALS1 201131_s_at CDH1 201131_s_at CDH1 201131_s_at CDH1 201131_s_at CDH1 201160_s_at CSDA 201160_s_at CSDA 201160_s_at CSDA 201160_s_at CSDA 201161_s_at CSDA 201161_s_at CSDA 201161_s_at CSDA 201161_s_at CSDA 201170_s_at BHLHB2 201170_s_at BHLHB2 201170_s_at BHLHB2 201417_at SOX4 201417_at SOX4 201417_at SOX4 201417_at SOX4 201565_s_at ID2 201565_s_at ID2 201565_s_at ID2 201565_s_at ID2 201839_s_at TACSTD1 201839_s_at TACSTD1 201839_s_at TACSTD1 201839_s_at TACSTD1 201939_at PLK2 201939_at PLK2 201939_at PLK2 201939_at PLK2 202075_s_at PLTP 202075_s_at PLTP 202075_s_at PLTP 202208_s_at ARL7 202208_s_at ARL7 202208_s_at ARL7 202363_at SPOCK 202363_at SPOCK 202391_at BASP1 202391_at BASP1 202391_at BASP1 202391_at BASP1 202551_s_at CRIM1 202551_s_at CRIM1 202551_s_at CRIM1 202733_at P4HA2 202790_at GABARAP 202790_at GABARAP 202790_at GABARAP 202790_at GABARAP 202826_at SPINT1 202826_at SPINT1 202826_at SPINT1 202839_s_at NDUFB7 203029_s_at PTPRN2 203029_s_at PTPRN2 203029_s_at PTPRN2 203029_s_at PTPRN2 203153_at IFIT1 203153_at IFIT1 203186_s_at S100A4 203186_s_at S100A4 203186_s_at S100A4 203186_s_at S100A4 203215_s_at MYO6 203215_s_at MYO6 203215_s_at MYO6 203215_s_at MYO6 203421_at TP53I11 203421_at TP53I11 203421_at TP53I11 203476_at TPBG 203476_at TPBG 203476_at TPBG 203476_at TPBG 203559_s_at ABP1 203828_s_at NK4 203887_s_at THBD 203888_at THBD 203962_s_at NEBL 203962_s_at NEBL 203962_s_at NEBL 203962_s_at NEBL 204103_at CCL4 204103_at CCL4 204103_at CCL4 204114_at NID2 204114_at NID2 204114_at NID2 204114_at NID2 204271_s_at EDNRB 204271_s_at EDNRB 204271_s_at EDNRB 204271_s_at EDNRB 204285_s_at PMAIP1 204285_s_at PMAIP1 204285_s_at PMAIP1 204285_s_at PMAIP1 204286_s_at PMAIP1 204286_s_at PMAIP1 204286_s_at PMAIP1 204288_s_at ARGBP2 204288_s_at ARGBP2 204288_s_at ARGBP2 204288_s_at ARGBP2 204374_s_at GALK1 204374_s_at GALK1 204430_s_at SLC2A5 204430_s_at SLC2A5 204430_s_at SLC2A5 204430_s_at SLC2A5 204439_at C1orf29 204439_at C1orf29 204439_at C1orf29 204439_at C1orf29 204469_at PTPRZ1 204469_at PTPRZ1 204469_at PTPRZ1 204560_at FKBP5 204560_at FKBP5 204560_at FKBP5 1st Recursive Clustering 2nd Recursive Clustering 3rd Recursive Clustering 4th Recursive Clustering Probe ID Gene Name Probe ID Gene Name Probe ID Gene Name Probe ID Gene Name 204641_at NEK2 204661_at CDW52 204661_at CDW52 204661_at CDW52 204661_at CDW52 204748_at PTGS2 204748_at PTGS2 204748_at PTGS2 204748_at PTGS2 204766_s_at NUDT1 204766_s_at NUDT1 204766_s_at NUDT1 204777_s_at MAL 204777_s_at MAL 204777_s_at MAL 204798_at MYB 204798_at MYB 204798_at MYB 204823_at NAV3 204823_at NAV3 204823_at NAV3 204836_at GLDC 204836_at GLDC 204836_at GLDC 204960_at PTPRCAP 204960_at PTPRCAP 204960_at PTPRCAP 204960_at PTPRCAP 205081_at CRIP2 205081_at CRIP2 205081_at CRIP2 205081_at CRIP2 205110_s_at FGF13 205110_s_at FGF13 205110_s_at FGF13 205110_s_at FGF13 205114_s_at CCL3 205114_s_at CCL3 205114_s_at CCL3 205122_at TMEFF1 205122_at TMEFF1 205122_at TMEFF1 205124_at MEF2B 205124_at MEF2B 205124_at MEF2B 205363_at BBOX1 205363_at BBOX1 205363_at BBOX1 205363_at BBOX1 205399_at DCAMKL1 205399_at DCAMKL1 205399_at DCAMKL1 205399_at DCAMKL1 205404_at HSD11B1 205433_at BCHE 205449_at HSU79266 205449_at HSU79266 205449_at HSU79266 205848_at GAS2 205848_at GAS2 205848_at GAS2 205902_at KCNN3 205902_at KCNN3 205902_at KCNN3 205902_at KCNN3 205967_at HIST1H4F 205968_at KCNS3 205968_at KCNS3 205968_at KCNS3 205968_at KCNS3 205983_at DPEP1 205983_at DPEP1 205997_at ADAM28 205997_at ADAM28 205997_at ADAM28 205997_at ADAM28 206045_s_at NOL4 206045_s_at NOL4 206045_s_at NOL4 206204_at GRB14 206204_at GRB14 206204_at GRB14 206204_at GRB14 206255_at BLK 206255_at BLK 206255_at BLK 206359_at SOCS3 206359_at SOCS3 206363_at MAF 206363_at MAF 206363_at MAF 206363_at MAF 206372_at MYF6 206372_at MYF6 206372_at MYF6 206394_at MYBPC2 206394_at MYBPC2 206394_at MYBPC2 206394_at MYBPC2 206456_at GABRA5 206461_x_at MT1H 206461_x_at MT1H 206461_x_at MT1H 206525_at GABRR1 206574_s_at PTP4A3 206574_s_at PTP4A3 206574_s_at PTP4A3 206574_s_at PTP4A3 206595_at CST6 206595_at CST6 206595_at CST6 206595_at CST6 206626_x_at SSX1 206640_x_at GAGE5 206762_at KCNA5 206762_at KCNA5 206762_at KCNA5 206762_at KCNA5 206834_at HBD 206834_at HBD 206834_at HBD 206834_at HBD 206843_at CRYBA4 206843_at CRYBA4 206843_at CRYBA4 206843_at CRYBA4 206897_at GAGEB1 206991_s_at CCR5 206991_s_at CCR5 206991_s_at CCR5 206991_s_at CCR5 207076_s_at ASS 207076_s_at ASS 207076_s_at ASS 207076_s_at ASS 207086_x_at GAGE5 207100_s_at VAMP1 207100_s_at VAMP1 207100_s_at VAMP1 1st Recursive Clustering 2nd Recursive Clustering 3rd Recursive Clustering 4th Recursive Clustering Probe ID Gene Name Probe ID Gene Name Probe ID Gene Name Probe ID Gene Name 207101_at VAMP1 207101_at VAMP1 207101_at VAMP1 207104_x_at LILRB1 207104_x_at LILRB1 207104_x_at LILRB1 207191_s_at ISLR 207191_s_at ISLR 207191_s_at ISLR 207337_at CTAG2 207339_s_at LTB 207339_s_at LTB 207339_s_at LTB 207339_s_at LTB 207414_s_at PACE4 207493_x_at SSX2 207663_x_at GAGE3 207666_x_at SSX3 207666_x_at SSX3 207666_x_at SSX3 207706_at USH2A 207706_at USH2A 207738_s_at NCKAP1 207738_s_at NCKAP1 207738_s_at NCKAP1 207739_s_at GAGE2 207826_s_at ID3 207826_s_at ID3 207826_s_at ID3 207918_s_at TSPY1 208029_s_at LAPTM4B 208029_s_at LAPTM4B 208029_s_at LAPTM4B 208112_x_at EHD1 208112_x_at EHD1 208155_x_at GAGE5 208235_x_at GAGE5 208456_s_at RRAS2 208456_s_at RRAS2 208456_s_at RRAS2 208502_s_at PITX1 208502_s_at PITX1 208502_s_at PITX1 208502_s_at PITX1 208553_at HIST1H1E 208553_at HIST1H1E 208553_at HIST1H1E 208553_at HIST1H1E 208580_x_at HIST1H4J 208580_x_at HIST1H4J 208580_x_at HIST1H4J 208581_x_at MT1X 208581_x_at MT1X 208581_x_at MT1X 208581_x_at MT1X 208851_s_at THY1 208893_s_at DUSP6 208893_s_at DUSP6 208893_s_at DUSP6 208932_at PPP4C 208932_at PPP4C 208932_at PPP4C 209013_x_at TRIO 209013_x_at TRIO 209013_x_at TRIO 209101_at CTGF 209101_at CTGF 209101_at CTGF 209109_s_at TM4SF6 209109_s_at TM4SF6 209109_s_at TM4SF6 209120_at NR2F2 209120_at NR2F2 209120_at NR2F2 209121_x_at NR2F2 209121_x_at NR2F2 209121_x_at NR2F2 209173_at AGR2 209173_at AGR2 209173_at AGR2 209173_at AGR2 209289_at NFIB 209289_at NFIB 209290_s_at NFIB 209301_at CA2 209301_at CA2 209301_at CA2 209301_at CA2 209309_at AZGP1 209309_at AZGP1 209309_at AZGP1 209309_at AZGP1 209368_at EPHX2 209368_at EPHX2 209368_at EPHX2 209368_at EPHX2 209374_s_at IGHM; MU 209374_s_at IGHM; MU 209374_s_at IGHM; MU 209374_s_at IGHM; MU 209485_s_at OSBPL1A 209485_s_at OSBPL1A 209485_s_at OSBPL1A 209621_s_at PDLIM3 209621_s_at PDLIM3 209621_s_at PDLIM3 209636_at NFKB2 209636_at NFKB2 209636_at NFKB2 209636_at NFKB2 209656_s_at TM4SF10 209656_s_at TM4SF10 209656_s_at TM4SF10 209656_s_at TM4SF10 209696_at FBP1 209696_at FBP1 209696_at FBP1 209696_at FBP1 209735_at ABCG2 209735_at ABCG2 209735_at ABCG2 209739_s_at DXS1283E 209739_s_at DXS1283E 209739_s_at DXS1283E 209757_s_at MYCN 209757_s_at MYCN 209757_s_at MYCN 209757_s_at MYCN 209785_s_at PLA2G4C 209785_s_at PLA2G4C 209785_s_at PLA2G4C 1st Recursive Clustering 2nd Recursive Clustering 3rd Recursive Clustering 4th Recursive Clustering Probe ID Gene Name Probe ID Gene Name Probe ID Gene Name Probe ID Gene Name 209795_at CD69 209795_at CD69 209795_at CD69 209795_at CD69 209958_s_at B1 209958_s_at B1 209958_s_at B1 209958_s_at B1 210152_at LILRB4 210170_at PDLIM3 210170_at PDLIM3 210170_at PDLIM3 210258_at RGS13 210258_at RGS13 210258_at RGS13 210432_s_at SCN3A 210432_s_at SCN3A 210432_s_at SCN3A 210432_s_at SCN3A 210497_x_at SSX2 210538_s_at BIRC3 210538_s_at BIRC3 210538_s_at BIRC3 210546_x_at CTAG1 210997_at HGF 210997_at HGF 210997_at HGF 210997_at HGF 210998_s_at HGF 210998_s_at HGF 210998_s_at HGF 210998_s_at HGF 211322_s_at SARDH 211322_s_at SARDH 211336_x_at LILRB1 211341_at POU4F1 211341_at POU4F1 211341_at POU4F1 211341_at POU4F1 211518_s_at BMP4 211518_s_at BMP4 211518_s_at BMP4 211518_s_at BMP4 211596_s_at LRIG1 211596_s_at LRIG1 211596_s_at LRIG1 211596_s_at LRIG1 211674_x_at CTAG1 211737_x_at PTN 211821_x_at GYPA 211821_x_at GYPA 211821_x_at GYPA 211821_x_at GYPA 212012_at D2S448 212012_at D2S448 212012_at D2S448 212012_at D2S448 212013_at D2S448 212013_at D2S448 212013_at D2S448 212013_at D2S448 212190_at SERPINE2 212190_at SERPINE2 212190_at SERPINE2 212390_at PDE4DIP 212390_at PDE4DIP 212390_at PDE4DIP 212589_at RRAS2 212589_at RRAS2 212589_at RRAS2 212724_at ARHE 212724_at ARHE 212724_at ARHE 212724_at ARHE 212827_at IGHM; MU 212827_at IGHM; MU 212827_at IGHM; MU 213032_at NFIB 213326_at VAMP1 213326_at VAMP1 213326_at VAMP1 213369_at PCDH21 213369_at PCDH21 213369_at PCDH21 213556_at R28379 213967_at LOC138046 213967_at LOC138046 213967_at LOC138046 214146_s_at PPBP 214146_s_at PPBP 214146_s_at PPBP 214228_x_at TNFRSF4 214228_x_at TNFRSF4 214228_x_at TNFRSF4 214254_at MAGEA4 214428_x_at C4A 214428_x_at C4A 214428_x_at C4A 214428_x_at C4A 214463_x_at HIST1H4K 214463_x_at HIST1H4K 214463_x_at HIST1H4K 214463_x_at HIST1H4K 214476_at TFF2 214476_at TFF2 214476_at TFF2 214476_at TFF2 214612_x_at MAGEA6 214612_x_at MAGEA6 214612_x_at MAGEA6 214651_s_at HOXA9 214651_s_at HOXA9 214651_s_at HOXA9 214651_s_at HOXA9 214667_s_at TP53I11 214667_s_at TP53I11 214667_s_at TP53I11 215025_at NTRK3 215025_at NTRK3 215118_s_at MGC27165 215118_s_at MGC27165 215118_s_at MGC27165 215118_s_at MGC27165 215356_at FLJ13072 215356_at FLJ13072 215356_at FLJ13072 215388_s_at HFL1 215388_s_at HFL1 215388_s_at HFL1 215733_x_at CTAG2 215733_x_at CTAG2 215733_x_at CTAG2 215733_x_at CTAG2 216063_at HBBP1 216063_at HBBP1 216471_x_at SSX2 1st Recursive Clustering 2nd Recursive Clustering 3rd Recursive Clustering 4th Recursive Clustering Probe ID Gene Name Probe ID Gene Name Probe ID Gene Name Probe ID Gene Name 217165_x_at MT1F 217165_x_at MT1F 217165_x_at MT1F 217339_x_at CTAG1 217418_x_at MS4A1 217418_x_at MS4A1 217418_x_at MS4A1 217418_x_at MS4A1 217771_at GOLPH2 217771_at GOLPH2 217771_at GOLPH2 217865_at RNF130 217865_at RNF130 217865_at RNF130 217865_at RNF130 217977_at SEPX1 217977_at SEPX1 218223_s_at CKIP-1 218223_s_at CKIP-1 218223_s_at CKIP-1 218589_at P2RY5 218589_at P2RY5 218589_at P2RY5 218589_at P2RY5 218623_at HMP19 218623_at HMP19 218678_at FLJ21841 218678_at FLJ21841 218706_s_at NS3TP2 218706_s_at NS3TP2 218706_s_at NS3TP2 218839_at HEY1 218839_at HEY1 218839_at HEY1 218839_at HEY1 218952_at PCSK1N 218952_at PCSK1N 218952_at PCSK1N 219121_s_at FLJ20171 219121_s_at FLJ20171 219121_s_at FLJ20171 219121_s_at FLJ20171 219247_s_at ZDHHC14 219247_s_at ZDHHC14 219247_s_at ZDHHC14 219247_s_at ZDHHC14 219274_at TM4SF12 219274_at TM4SF12 219377_at C18orf11 219377_at C18orf11 219377_at C18orf11 219555_s_at BM039 219555_s_at BM039 219659_at ATP8A2 219659_at ATP8A2 219659_at ATP8A2 219659_at ATP8A2 219737_s_at PCDH9 219737_s_at PCDH9 219737_s_at PCDH9 219737_s_at PCDH9 219918_s_at ASPM 219918_s_at ASPM 220057_at GAGED2 220057_at GAGED2 220179_at DPEP3 220179_at DPEP3 220179_at DPEP3 220377_at HSPC053 220377_at HSPC053 220377_at HSPC053 220377_at HSPC053 220994_s_at STXBP6 220994_s_at STXBP6 220994_s_at STXBP6 220994_s_at STXBP6 221035_s_at TEX14 221035_s_at TEX14 221035_s_at TEX14 221310_at FGF14 221310_at FGF14 221310_at FGF14 221310_at FGF14 221467_at MC4R 221467_at MC4R 221467_at MC4R 221467_at MC4R 221581_s_at WBSCR5 221581_s_at WBSCR5 221602_s_at TOSO 221602_s_at TOSO 221602_s_at TOSO 221602_s_at TOSO 221702_s_at BLP2 221702_s_at BLP2 221702_s_at BLP2 221810_at ESTs 221810_at ESTs 221810_at ESTs 221841_s_at 221841_s_at KLF4 221841_s_at KLF4 221879_at MGC4809 221879_at MGC4809 221911_at ETV1 221911_at ETV1 221911_at ETV1 221911_at ETV1 221920_s_at MSCP 221920_s_at MSCP 221920_s_at MSCP 221920_s_at MSCP 222068_s_at LOC123872 222068_s_at LOC123872 222068_s_at LOC123872 222221_x_at EHD1 222221_x_at EHD1 222221_x_at EHD1 34210_at CDW52 64408_s_at MGC4809 Supplementary table 3. Genes involved in biosynthesis / transport / catabolism that are upregaulated in H-MM compared to NH-MM

Probe Set ID P-value Gene Symbol Chormosome Process Location 203281_s_at 0.00612 UBE1L 3 Protein Catabolism 221654_s_at 0.000761 USP3 15 Protein Catabolism 218306_s_at 0.00818 HERC1 15 Protein Catabolism 204583_x_at 0.00082 KLK3 19 Protein Catabolism 200063_s_at 0.000761 NPM1 5 Protein Transport 200960_x_at 0.00393 CLTA 9 Protein Transport 212699_at 0.00134 SCAMP5 9 Protein Transport 200705_s_at 0.0094 EEF1B2 2 Protein Biosynthesis 213801_x_at 0.00666 RPSA 3 Protein Biosynthesis 200823_x_at 0.000853 RPL29 3 Protein Biosynthesis 213588_x_at 0.000383 RPL14 3 Protein Biosynthesis 221475_s_at 0.00275 RPL15 3 Protein Biosynthesis 200674_s_at 0.00519 RPL32 3 Protein Biosynthesis 214143_x_at 0.000979 RPL24 3 Protein Biosynthesis 200013_at 8.02E-05 RPL24 3 Protein Biosynthesis 200912_s_at 0.000959 EIF4A2 3 Protein Biosynthesis 213687_s_at 0.00365 RPL35A 3 Protein Biosynthesis 201517_at 0.00195 NCBP2 3 Protein Biosynthesis 200092_s_at 0.00256 RPL37 5 Protein Biosynthesis 200926_at 0.00811 RPS23 5 Protein Biosynthesis 208645_s_at 0.00257 RPS14 5 Protein Biosynthesis 211623_s_at 0.00224 FBL 6 Protein Biosynthesis 217740_x_at 0.00076 RPL7A 9 Protein Biosynthesis 200081_s_at 0.000117 RPS6 9 Protein Biosynthesis 200002_at 0.000506 RPL35 9 Protein Biosynthesis 203034_s_at 0.00099 RPL27A 11 Protein Biosynthesis 200018_at 0.00179 RPS13 11 Protein Biosynthesis 211345_x_at 0.00666 EEF1G 11 Protein Biosynthesis 208692_at 0.000553 RPS3 11 Protein Biosynthesis 200763_s_at 0.0055 RPLP1 11 Protein Biosynthesis 213356_x_at 0.00233 HNRPA1 12 Protein Biosynthesis 200012_x_at 0.0024 RPL21 13 Protein Biosynthesis 221688_s_at 0.00425 IMP3 15 Protein Biosynthesis 217915_s_at 0.00151 C15orf15 15 Protein Biosynthesis 208985_s_at 0.00508 EIF3S1 15 Protein Biosynthesis 201665_x_at 0.00358 RPS17 15 Protein Biosynthesis 200909_s_at 0.00241 RPLP2 15 Protein Biosynthesis 200089_s_at 0.00145 RPL4 15 Protein Biosynthesis 211558_s_at 0.00152 DHPS 19 Protein Biosynthesis 200094_s_at 0.00396 EEF2 19 Protein Biosynthesis 208887_at 0.00201 EIF3S4 19 Protein Biosynthesis 221700_s_at 0.000469 UBA52 19 Protein Biosynthesis 221692_s_at 0.0022 MRPL34 19 Protein Biosynthesis 200715_x_at 0.000101 RPL13A 19 Protein Biosynthesis 219762_s_at 0.000521 RPL36 19 Protein Biosynthesis 200819_s_at 0.00149 RPS15 19 Protein Biosynthesis 210501_x_at 0.00768 EIF3S12 19 Protein Biosynthesis 202649_x_at 0.00036 RPS19 19 Protein Biosynthesis 200022_at 0.000579 RPL18 19 Protein Biosynthesis 200003_s_at 0.00116 RPL28 19 Protein Biosynthesis 213890_x_at 0.00864 RPS16 19 Protein Biosynthesis 214317_x_at 0.00133 RPS9 19 Protein Biosynthesis 201221_s_at 0.00425 SNRP70 19 Protein Biosynthesis 217336_at 0.00991 RPS10 20 Protein Biosynthesis 217846_at 0.00811 QARS 3p Protein Biosynthesis Supplementary table 4. Genes involved in protein biosynthesis / transport / catabolism that are down-regulated in H-MM compared to NH-MM

Probe Set ID P-value Gene Symbol Chormosome Process Location 201381_x_at 0.00427 CACYBP 1 Protein Catabolism 205997_at 0.00533 ADAM28 8 Protein Catabolism 201351_s_at 0.000853 YME1L1 10 Protein Catabolism 211764_s_at 0.0015 UBE2D1 10 Protein Catabolism 212229_s_at 0.00732 FBXO21 12 Protein Catabolism 201962_s_at 0.00646 RNF41 12 Protein Catabolism 200083_at 0.000105 USP22 17 Protein Catabolism 212155_at 0.000226 RNF187 17 Protein Catabolism 218564_at 0.00435 RFWD3 19 Protein Catabolism 220731_s_at 0.0022 NECAP2 1 Protein Transport 208684_at 0.000867 COPA 1 Protein Transport 201707_at 0.00423 PEX19 1 Protein Transport 212246_at 0.00594 MCFD2 2 Protein Transport 200945_s_at 0.000282 SEC31L1 4 Protein Transport 212160_at 0.00276 XPOT 12 Protein Transport 214209_s_at 0.00566 ABCB9 12 Protein Transport 204427_s_at 0.00358 RNP24 12 Protein Transport 211458_s_at 0.00457 GABARAPL1 15 Protein Transport 217727_x_at 0.000403 VPS35 16 Protein Transport 209046_s_at 0.000959 GABARAPL2 16 Protein Transport 217913_at 0.00784 VPS4A 16 Protein Transport 201582_at 0.00427 SEC23B 20 Protein Transport 201651_s_at 5.39E-05 PACSIN2 22 Protein Transport 206052_s_at 0.00625 SLBP 4 Protein Biosynthesis 208770_s_at 0.00544 EIF4EBP2 10 Protein Biosynthesis 209233_at 0.0022 C2F 12 Protein Biosynthesis 201632_at 0.00612 EIF2B1 12 Protein Biosynthesis 205158_at 0.0024 RNASE4 14 Protein Biosynthesis 219575_s_at 0.00269 COG8 16 Protein Biosynthesis 202021_x_at 0.000892 SUI1 17 Protein Biosynthesis

Supplementary table 5. GSEA analysis of genes associated with Cluster 1

NAME NES p-value

Functional Gene Sets BRCA_PROGNOSIS_NEG 2.22 0.00 VANTVEER_GOOD_OUTCOME_BREAST 2.15 0.00 SHIPP_DLBCL_UP 2.10 0.00 P21_ALL_DN 2.08 0.00 SCHUMACHER_MYC_P493_TET_UP 2.03 0.00 ADIP_DIFF_CLUSTER4 2.00 0.00 MANALO_HYPOXIA_DOWN 2.00 0.00 CELL_CYCLE_KEGG 1.99 0.00 OLDAGE_DN 1.97 0.00 E2F1_TARGETS_CHIP 1.97 0.00 SERUM_FIBROBLAST_CELLCYCLE 1.96 0.00 CANCER_UNDIFFERENTIATED_META_UP 1.94 0.00 COLLER_MYC_293_UP 1.93 0.00 CELL_CYCLE 1.93 0.00 P21_P53_ALL_DN 1.91 0.00 PENG_GLUTAMINE_DOWN 1.91 0.00 UNDERHILL_PROLIFERATION 1.90 0.00 BRENTANI_REPAIR 1.90 0.00 P21_P53_MIDDLE_DN 1.89 0.00 G1_TO_S_CELL_CYCLE_REACTOME 1.89 0.00

Motif-Based Gene Sets SGCGSSAAA_V$E2F1DP2_01 1.96 0.00 V$E2F4DP2_01 1.90 0.00 V$E2F1DP1_01 1.90 0.00 V$E2F1DP2_01 1.90 0.00 V$E2F_02 1.88 0.00 V$E2F1_Q3 1.87 0.00 V$E2F4DP1_01 1.84 0.00 V$E2F1_Q6 1.80 0.00 V$E2F_01 1.74 0.00 KTGGYRSGAA_UNKNOWN 1.74 0.00 V$E2F_Q6 1.72 0.00 V$E2F_Q3_01 1.70 0.00 V$E2F_Q4_01 1.70 0.00 V$E2F_Q4 1.70 0.00 V$E2F_Q6_01 1.61 0.00 V$E2F1DP1RB_01 1.59 0.00 V$MYC_Q2 1.49 0.02 V$USF2_Q6 1.57 0.03 V$E2F_03 1.60 0.03 V$E2F1_Q4_01 1.67 0.03

Supplementary table 6. GSEA analysis of genes associated with Cluster 2

NAME NES p-value

Functional Gene Sets GPCRPATHWAY 0.50 0.00 TPOPATHWAY 0.53 0.00 NGFPATHWAY 0.55 0.00 IGF1_NIH3T3_UP 0.49 0.00 BRENTANI_TRANSCRIPTION_FACTORS 0.38 0.00 HYPOXIA_NORMAL_UP 0.35 0.00 UVC_TTD_8HR_UP 0.41 0.00 VEGF_MMMEC_3HRS_UP 0.39 0.00 MYOD_NIH3T3_UP 0.38 0.00 CMV_HCMV_TIMECOURSE_14HRS_UP 0.36 0.02 CREBPATHWAY 0.42 0.02 CHREBPPATHWAY 0.57 0.02 RAC1PATHWAY 0.50 0.02 POMEROY_DESMO_MD_UP 0.41 0.02 PDGFPATHWAY 0.47 0.02 CCR5PATHWAY 0.52 0.02 BIOPEPTIDESPATHWAY 0.43 0.03 PROLIF_GENES 0.22 0.03 AGUIRRE_PANCREAS_CHR17 0.50 0.04 FERRANDO_TAL1_UP 0.55 0.04

Motif-Based Gene Sets V$PPARA_02 0.40 0.00 V$LBP1_Q6 0.27 0.00 V$OCT1_04 0.27 0.00 V$TATA_01 0.28 0.00 V$GATA2_01 0.30 0.03 V$PAX3_B 0.33 0.03 V$HSF1_01 0.25 0.03 V$OCT1_07 0.26 0.03 V$STAT5A_03 0.26 0.04 V$FOXM1_01 0.25 0.04 V$LXR_Q3 0.31 0.04 V$MIF1_01 0.27 0.05

Supplementary table 7. GSEA analysis of genes associated with Cluster 3

NAME NES p-value

Functional Gene Sets TNFR2PATHWAY 2.04 0.00 BLEO_HUMAN_LYMPH_HIGH_24HRS_UP 2.00 0.00 TH1TH2PATHWAY 1.95 0.00 BRENTANI_SIGNALLING 1.93 0.00 DEATHPATHWAY 1.93 0.00 APOPTOSIS 1.91 0.00 CCR5PATHWAY 1.87 0.00 CXCR4PATHWAY 1.86 0.00 ECMPATHWAY 1.80 0.00 IDX_TSA_DN_CLUSTER5 1.79 0.00 SIG_CD40PATHWAYMAP 1.78 0.00 ST_GA13_PATHWAY 1.77 0.00 NFKBPATHWAY 1.77 0.00 UVC_LOW_ALL_DN 1.75 0.00 41BBPATHWAY 1.74 0.00 INFLAMMATORY_RESPONSE_PATHWAY 1.73 0.00 TGF_BETA_SIGNALING_PATHWAY 1.73 0.00 IL7PATHWAY 1.72 0.00 TNFA_5ENDOTHELIAL_UP 1.70 0.00

Motif-Based Gene Sets GGGNNTTTCC_V$NFKB_Q6_01 1.81 0.00 YKACATTT_UNKNOWN 1.57 0.01 V$PITX2_Q2 1.49 0.01 V$ICSBP_Q6 1.51 0.01 V$NFKAPPAB_01 1.47 0.01 V$SRY_02 1.41 0.01 V$SP1_Q2_01 1.58 0.01 V$NFKB_Q6_01 1.47 0.01 V$NFKB_C 1.49 0.01 V$AREB6_04 1.37 0.01 V$SP1_Q6_01 1.57 0.01 V$AML1_01 1.38 0.02 V$AML1_Q6 1.38 0.02 V$ISRE_01 1.43 0.02 AGCYRWTTC_UNKNOWN 1.40 0.02 V$OCT1_06 1.33 0.02 V$AREB6_03 1.41 0.02 RAAGNYNNCTTY_UNKNOWN 1.42 0.02 V$ETS2_B 1.37 0.02 WTTGKCTG_UNKNOWN 1.26 0.03 Supplementary table 8. GSEA analysis of genes associated with Cluster 4

NAME NES p-value

Functional Gene Sets ALKPATHWAY 1.69 0.00 WNT_TARGETS 1.57 0.00 MAGRANGEAS_LK_DOWN 1.57 0.02 AGED_MOUSE_NEOCORTEX_DN 1.58 0.04

Motif-Based Gene Sets V$AFP1_Q6 1.43 0.00 V$AHRARNT_01 1.58 0.01 CTGYNNCTYTAA_UNKNOWN 1.56 0.01 V$PAX4_04 1.38 0.01 V$ER_Q6_01 1.31 0.02 V$PR_01 1.36 0.03 V$AR_03 1.52 0.03 V$GATA_Q6 1.41 0.03 RNTCANNRNNYNATTW_UNKNOWN 1.44 0.04 V$TAL1ALPHAE47_01 1.35 0.04 YTCCCRNNAGGY_UNKNOWN 1.39 0.04