EGAGenomicsN/Ahttps://ega-archive.org/datasets/EGAD00001008837230EGA dataset EGAD00001008837EGAMelanoma of the skin is a common cancer only in Europeans, whereas it arises in internal body surfaces (mucosal sites) and on the hands and feet (acral sites) in people throughout the world. Here we report analysis of whole-genome sequences from cutaneous, acral and mucosal subtypes of melanoma. The heavily mutated landscape of coding and non-coding mutations in cutaneous melanoma resolved novel signatures of mutagenesis attributable to ultraviolet radiation. However, acral and mucosal melanomas were dominated by structural changes and mutation signatures of unknown aetiology, not previously identified in melanoma. The number of genes affected by recurrent mutations disrupting non-coding sequences was similar to that affected by recurrent mutations to coding sequences. Significantly mutated genes included BRAF, CDKN2A, NRAS and TP53 in cutaneous melanoma, BRAF, NRAS and NF1 in acral melanoma and SF3B1 in mucosal melanoma. Mutations affecting the TERT promoter were the most frequent of all; however, neither they nor ATRX mutations, which correlate with alternative telomere lengthening, were associated with greater telomere length. Most melanomas had potentially actionable mutations, most in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways. The whole-genome mutation landscape of melanoma reveals diverse carcinogenic processes across its subtypes, some unrelated to sun exposure, and extends potential involvement of the non-coding genome in its pathogenesis.Whole-genome landscapes of major melanoma subtypes.Hayward Nicholas K NK, Wilmott James S JS, Waddell Nicola N, Johansson Peter A PA, Field Matthew A MA, Nones Katia K, Patch Ann-Marie AM, Kakavand Hojabr H, Alexandrov Ludmil B LB, Burke Hazel H, Jakrot Valerie V, Kazakoff Stephen S, Holmes Oliver O, Leonard Conrad C, Sabarinathan Radhakrishnan R, Mularoni Loris L, Wood Scott S, Xu Qinying Q, Waddell Nick N, Tembe Varsha V, Pupo Gulietta M GM, De Paoli-Iseppi Ricardo R, Vilain Ricardo E RE, Shang Ping P, Lau Loretta M S LMS, Dagg Rebecca A RA, Schramm Sarah-Jane SJ, Pritchard Antonia A, Dutton-Regester Ken K, Newell Felicity F, Fitzgerald Anna A, Shang Catherine A CA, Grimmond Sean M SM, Pickett Hilda A HA, Yang Jean Y JY, Stretch Jonathan R JR, Behren Andreas A, Kefford Richard F RF, Hersey Peter P, Long Georgina V GV, Cebon Jonathan J, Shackleton Mark M, Spillane Andrew J AJ, Saw Robyn P M RPM, López-Bigas Núria N, Pearson John V JV, Thompson John F JF, Scolyer Richard A RA, Mann Graham J GJMAPK-activated protein kinase 2, ribonucleic acid, Acid, DmMAPKAPK-2, RNA, Ribonucleic, ribose nucleic acid, Non Polyadenylated RNA, ribonucleic acids, Non-Polyadenylated, AA589381, MK2, AA960234, RNS, Prkmk2, Ribonucleic Acid, MAPKAPK-2, MAPKAP-K2, dMK2, RNA Gene Products., MAPKAP, Non-Polyadenylated RNA, Voltage-gated potassium channel subunit Kv1.2, 2.7.11.1, MK-2, CG3086, yeast nucleic acid, Ribonukleinsaeure, Gene Products, pentosenucleic acids, Rps6kc1, Ribonucleic acids, MAPKAP kinase 2, MEK2, Non Polyadenylated, DmelCG3086melanoma (disease), malignant melanoma, Melanomas, whole genome, Melanoma, Malignant Melanomas, melanoma, Naevocarcinoma., Genomes, Malignant, malignant, Malignant Melanomamelanoma (disease), malignant melanoma, Melanomas, Melanoma, Malignant Melanomas, melanoma, Naevocarcinoma., Malignant, malignant, Malignant Melanoma145kDa, DmErk, extracellular signal-regulated kinase activity, pp44mapk, Materials, telomere, p19<ARF>, Tyro5, raf, Progress Reports, ALPHA-thalassemia/mental retardation syndrome, Tumor, Xnp, XNP, hTRT, Prp4 protein kinase activity, Mutations, DmelCG8318, unspecified, LeMPK3, subungual melanoma, ATP-protein transphosphorylase activity, Summary Report, type I, p44mpk, bbl, ATP:protein phosphotransferase (non-specific) activity, nuclear chromosome, Dp38, ARF-INK4a, AA120551, Protein Kinases, Kinase, SAPK2, p16(INK4a), SEM, Sem, peripheral type, MAP-k, E030030H24Rik, stimulation by symbiont of host programmed cell death, Progress Report, Genomes, BCC7, Draf-1, pp42, EK5, Dsor2, MALIG MELANOMA SKIN NEC, sem, D-raf1, high frequency, Field Reports, INSDC_feature:telomere, ATP Phosphotransferases, Hp1bp38, Tumors, p82 kinase activity, ERK-A, dpERK, dpErk, anatomical protrusion, l(1)phl, mutagenesis, betaIIPKC, DmMAPK, Alpha thalassemia mental retardation syndrome, Malignant Melanomas, Alpha thalassemia intellectual disability syndrome, PMK-2, dp-ERK, PMK-1, cRaf, telomeric sequence, SHS, PMK-3, Wee-kinase activity, Sap155, Benign, malignant melanoma of skin, stage unspecified, Recklinghausen's disease, MRXS3, pMAPK, pMapK, bfy, v-Raf, 155kDa, Malignant melanoma of skin of other and unspecified parts of face, DmERKA, l(1)pole hole, whole organism, rl/MAPK, TCS1, CRAF, Field, NRAS, non-specific serine/threonine protein kinase activity, Benign Neoplasms, ZNF-HX, l(2)41Ac, whole genome, l(1)polehole, D-raf, Malignant Neoplasms, ALPHA-thalassemia/intellectual disability syndrome, Report, CT34260, CMD1NN, dpERk, cutaneous (skin) melanoma, Material, MITOGEN-ACTIVATED PROTEIN KINASE, serine-specific protein kinase activity, activation by symbiont of host programmed cell death, Koerper, HIPK2, SAPK, cytidine 3', bhy, WSS, EG:BACH48C10.3, BB129353, mitogen-activated protein kinase 1, Wee 1-like kinase activity, INK4A, AA473386, SF3b1, CDKN2, MAL MELANOM FACE NEC/NOS, TA-8, telomeric region, X-linked, glycogen synthase A kinase activity, Malignant melanoma of skin (disorder), INK4, Neoplasms, regulation by symbiont of host system process, glycogen synthase kinase 3 activity, number, 12559, F14N23.9, DRaf, LFS1, draf, phosphorylase b kinase kinase activity, unspecified (disorder), EK2-1, palmar/plantar melanoma, site unspecified, melanoma (disease), induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, ALPS4, causality., TP2, ribosomal protein S6 kinase II activity, Malignant Melanoma (of Skin), D-RAF, D-Raf, Erk, ERK, protein-serine kinase activity, skin, malignant trunk melanoma, Naevocarcinoma, STK32, PCBC, C87398, Phl, Nf-1, NFNS, Mitogen Activated Protein Kinases, VRNF, erk, melanoma (disease) of zone of skin, Neoplasias, Malignant melanoma of other specified sites of skin, protein-cysteine kinase activity, Hpr kinase activity, p19ARF, Draf, rll, skin melanoma, STK26, Investigative Reports, NF1, NF-1, nf1, p38-2, von Reklinghausen disease, myelin basic protein kinase activity, Cancer, ALM, Malignant Melanoma of Skin, TP16, DRT, Malignant Neoplasm, NRAS1, hemolysin activity, body, ATR2, raf-1, Melanoma of skin, stress-activated kinase activity, MAP-2 kinase activity, BRAF1, whole body, TRT, protein serine kinase activity, p19-lt-ARF-gt-, p16INK4a, MDS, protein phosphokinase activity, PRP10, Melanoma of Skin, MT, ATRX, PKA, PKC, P14ARF, Malignant Melanoma, stress-activated protein kinase activity, Research Reports, chemical analysis, mapk2, mapk1, Neoplasm, Mutageneses, Prp10, Hsh155, AA990557, Skin, INSDC_feature:regulatory, protein kinase p58 activity, P16INK4A, AA409119, serine/threonine protein kinase activity, Nondeletion type, primary cancer, CG12559, Malignant Cutaneous Melanoma, dpERK1, Von Recklinghausen disease, Cancers, dsk1, malignant tumor, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, Hands, INK4a-ARF, l(1)polehole/draf, DXHXS6677E, Hp1bp2, Rad54, Reports, dpMAPK, Braf2, malignant cutaneous melanoma, Feet, RAD54, ph, protein serine-threonine kinase activity, Neoplasia, SAP kinase activity, glycogen synthase kinase activity, Melanoma of the Skin, MTS1, SF3b145, c-Raf, protein kinase A activity, determination, Mpk2, Cus1, malignant scalp melanoma, positive regulation by symbiont of host non-apoptotic programmed cell death, p42mapk, Pctr1, Tp53, SR2-1, cancer of skin, Mitogen Activated Protein Kinase, XLMR hypotonic face syndrome, melanoma, Mitogen-Activated Protein, SAP145, 2610311M13Rik, hEST2, DKCB4, kinase-related transforming protein, pathogenesis, malignant melanoma of skin of trunk except scrotum, Arf, mitogen-activated protein kinase activity, ARF, SF3B145, Alpha-thalassemia-X-linked intellectual disability syndrome, animal, mpk1, Summary Reports, SF3b155, SF3b150, NCMS, Targ4, N-ras, acral lentiginous malignant melanoma of skin, Erk/Map kinase, DKCA2, DERK-A, MTS-1, type 1 neurofibromatosis, Malignant melanoma of other specified skin site (disorder), Craf1, E(sina)7, Rl, Raf kinase activity, 9930012E13Rik, Progress, [X]Malignant melanoma of skin, serine kinase activity, MP kinase activity, DERK, C230098H17, atypical protein kinase C activity, malignant neoplasm, malignant melanoma of skin of upper limb, MBP kinase II activity, mitogen-activated S6 kinase activity, P14, protein-aspartyl kinase activity, Malignancies, P16, dERK, D6Ertd631e, P19, P16-INK4A, ATP, TR, ATR, cutaneous melanoma, Mitogen-Activated, 6430402F14Rik, B-RAF1, MAP kinase 2 activity, melanoma of the skin, Mapk, MLM, CG8318, Erk1, ERK1, p16, ERK2, mapk1a, MM - Malignant melanoma of skin, Malignant melanoma of other specified skin site, malignant lower limb melanoma, M phase-specific cdc2 kinase activity, Melanoma, Investigative Report, mapk1b, MapK, malignant neck melanoma, MAPK, modulation by symbiont of host system process, Alpha-thalassemia/mental retardation syndrome, Genetic Materials, NOS, ATRX syndrome, serine protein kinase activity, DRaf1, dNF1, PRPF10, erk2, Genetic Material, mapk, l(1)G0475, phosphorylase B kinase kinase activity, ERKa, Transphosphorylases, malignant lip melanoma, RAFB1, malignant ear melanoma, BcDNA:RE08694, protein glutamyl kinase activity, l(2R)EMS45-39, Draf1, raf1, CAPB, MRXHF1, AA387315, DmelCG12559, common, SAP155, p38, RAD54L, DpErk, DpERK, 2810441F20Rik, ErkA, ERKA, hydroxyalkyl-protein kinase activity, WEE1Hu, MALIG MELANOMA SKIN NOS, spine, epsilon PKC, P53, telomeric DNA, p44, C110, Cistron, AV095280, Protein Kinase, pERK, rafl, F14N23_9, ribosomal S6 protein kinase activity, calcium/phospholipid-dependent protein kinase activity, GroupII, p53, NS6, Benign Neoplasm, NS5, NS7, Gene, neurofibromatosis, Malignant, zone of skin melanoma (disease), 4833408C14Rik, protrusion, Proto-oncogene c-RAF, Hek5, Investigative, nondeletion type, HP1-BP38, SFM1, serine(threonine) protein kinase activity, Malignant melanoma of skin NOS (disorder), Stage Unspecified, mucosal melanoma, Phosphotransferase, Raf1, melanoma of skin, Malignant melanoma of skin, T-antigen kinase activity, galactosyltransferase-associated kinase activity, XH2, Mitogen-Activated Protein Kinase, telomeres, Genetic, Malignancy, DmelCG2845, xp42, zone of skin melanoma, causes, Transphosphorylase, p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, protein kinase (phosphorylating) activity, AI447451, Trp53, Ink4a|Arf, CMM9, Raf-1, l(1)raf, CMM2, JMS, ATMPK1, DmERK-A, TRP53, casein kinase (phosphorylating) activity, ert1, activation by organism of non-apoptotic programmed cell death in other organism, P16INK4, malignant, 2810001M05Rik, prkm2, prkm1, CT39192, l(1)2Fe, malignant melanoma of skin stage unspecified, Cistrons, Phosphotransferases, Xp53, Alpha-thalassemia/intellectual disability syndrome, neurofibromatosis type 1 microdeletion syndrome, p38delta, Melanomas, twitchin kinase activity, Raf/phl, 2.7.11.1, EST2, AP50 kinase activity, CMNS, MBP kinase I activity, Ink4a/Arf, Telomeres, B-raf, malignant melanoma (of skin), Xp42, Radiations, threonine-specific protein kinase activity, frequent, Kinases, mitogen activated kinase activity, malignant melanoma of ear and/or external auricular canal, Su(Raf)2B, CDK4I, B230398H18Rik, EY2-2, l(1)ph, cutaneous melanoma (disease), 11-29, malignant melanoma of skin of lower limb, D-ERK, D830050J10Rik, Braf-2, PFBMFT1, acral melanoma, Alpha-thalassemia X-linked intellectual disability syndrome, P19ARF, malignant upper limb melanoma, EPHT3, cardinality, AW494271, malignant melanoma, assay, RAF, Raf, Summary, Field Report, A-kinase activity, MAP kinase 1 activity, CG2845falseEGA_MELA_mk2_RNA - samplesIllumina RNASeq sequencing of tumour samples from 230 cases of melanoma2022-09-05 09:44:13EGAD00001008837960628467829EGAC00001000010EGAS00001001552