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Melanomics: Comprehensive Molecular Analysis of Normal and Neoplastic Melanocytes

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Melanoma

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Abstract

Cutaneous melanoma is the deadliest form of skin cancer. An immense understanding of this disease has emerged through the molecular characterization of melanocytes and melanomas, which has resulted in the development of therapies that have impacted patient outcomes. This chapter will review studies that have characterized the melanoma genome, transcriptome, as well as the epigenome of non-acral, cutaneous, and uveal melanoma. Specifically, first-generation sequencing findings that discovered many of the frequently mutated oncogenes and tumor suppressors in melanoma will be described. Subsequently, next-generation sequencing studies that revealed novel UV-induced driver mutations and frequent noncoding mutations will be covered. Finally, integrative analyses of melanoma across multiple data platforms that have led to the discovery of new biomarkers and increased our understanding of the molecular basis of this disease will be reviewed.

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References

  • Aalto Y, Eriksson L, Seregard S, Larsson O, Knuutila S (2001) Concomitant loss of chromosome 3 and whole arm losses and gains of chromosome 1, 6, or 8 in metastasizing primary uveal melanoma. Invest Ophthalmol Vis Sci 42:313–317

    CAS  PubMed  Google Scholar 

  • Aftab MN, Dinger ME, Perera RJ (2014) The role of microRNAs and long non-coding RNAs in the pathology, diagnosis, and management of melanoma. Arch Biochem Biophys 563:60–70

    Article  CAS  PubMed  Google Scholar 

  • Albino AP, Nanus DM, Mentle IR, Cordon-Cardo C, McNutt NS, Bressler J, Andreeff M (1989) Analysis of ras oncogenes in malignant melanoma and precursor lesions: correlation of point mutations with differentiation phenotype. Oncogene 4:1363–1374

    CAS  PubMed  Google Scholar 

  • Arafeh R, Qutob N, Emmanuel R, Keren-Paz A, Madore J, Elkahloun A, Wilmott JS, Gartner JJ, Di Pizio A, Winograd-Katz S et al (2015) Recurrent inactivating RASA2 mutations in melanoma. Nat Genet 47:1408–1410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Armanios M, Blackburn EH (2012) The telomere syndromes. Nat Rev Genet 13:693–704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asangani IA, Harms PW, Dodson L, Pandhi M, Kunju LP, Maher CA, Fullen DR, Johnson TM, Giordano TJ, Palanisamy N (2012) Genetic and epigenetic loss of microRNA-31 leads to feed-forward expression of EZH2 in melanoma. Oncotarget 3:1011

    Article  PubMed  PubMed Central  Google Scholar 

  • Azimi F, Scolyer RA, Rumcheva P, Moncrieff M, Murali R, McCarthy SW, Saw RP, Thompson JF (2012) Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol 30:2678–2683

    Article  PubMed  Google Scholar 

  • Baade P, Meng X, Youlden D, Aitken J, Youl P (2012) Time trends and latitudinal differences in melanoma thickness distribution in Australia, 1990–2006. Int J Cancer 130:170–178

    Article  CAS  PubMed  Google Scholar 

  • Balázs M, Ádám Z, Treszl A, Bégány Á, Hunyadi J, Ádány R (2001) Chromosomal imbalances in primary and metastatic melanomas revealed by comparative genomic hybridization. Cytometry 46:222–232

    Article  PubMed  Google Scholar 

  • Balch CM, Gershenwald JE, Soong S-J, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S et al (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206

    Article  PubMed  PubMed Central  Google Scholar 

  • Bardella C, Pollard PJ, Tomlinson I (2011) SDH mutations in cancer. Biochim Biophys Acta 1807:1432–1443

    Article  CAS  PubMed  Google Scholar 

  • Bastian BC (2014) The molecular pathology of melanoma: an integrated taxonomy of melanocytic neoplasia. Annu Rev Pathol 9:239–271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D (1998) Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res 58:2170–2175

    CAS  PubMed  Google Scholar 

  • Bastian BC, Kashani-Sabet M, Hamm H, Godfrey T, Moore DH 2nd, Brocker EB, LeBoit PE, Pinkel D (2000a) Gene amplifications characterize acral melanoma and permit the detection of occult tumor cells in the surrounding skin. Cancer Res 60:1968–1973

    CAS  PubMed  Google Scholar 

  • Bastian BC, LeBoit PE, Pinkel D (2000b) Mutations and copy number increase of HRAS in Spitz nevi with distinctive histopathological features. Am J Pathol 157:967–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bastian BC, Olshen AB, LeBoit PE, Pinkel D (2003) Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol 163:1765–1770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bell RJA, Rube HT, Kreig A, Mancini A, Fouse SD, Nagarajan RP, Choi S, Hong C, He D, Pekmezci M et al (2015) The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer. Science 348:1036–1039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bennett PE, Bemis L, Norris DA, Shellman YG (2013) miR in melanoma development: miRNAs and acquired hallmarks of cancer in melanoma. Physiol Genomics 45:1049–1059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berger MF, Hodis E, Heffernan TP, Deribe YL, Lawrence MS, Protopopov A, Ivanova E, Watson IR, Nickerson E, Ghosh P et al (2012) Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 485:502–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bittner M, Meltzer P, Chen Y, Jiang Y, Seftor E, Hendrix M, Radmacher M, Simon R, Yakhini Z, Ben-Dor A et al (2000) Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 406:536–540

    Article  CAS  PubMed  Google Scholar 

  • Brash DE (2015) UV signature mutations. Photochem Photobiol 91:15–26

    Article  CAS  PubMed  Google Scholar 

  • Brown CJ, Hendrich BD, Rupert JL, Lafrenière RG, Xing Y, Lawrence J, Willard HF (1992) The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell 71:527–542

    Article  CAS  PubMed  Google Scholar 

  • Brunner G, Reitz M, Schwipper V, Tilkorn H, Lippold A, Biess B, Suter L, Atzpodien J (2008) Increased expression of the tumor suppressor PLZF is a continuous predictor of long-term survival in malignant melanoma patients. Cancer Biother Radiopharm 23:451–459

    Article  CAS  PubMed  Google Scholar 

  • Brunner G, Reitz M, Heinecke A, Lippold A, Berking C, Suter L, Atzpodien J (2013) A nine-gene signature predicting clinical outcome in cutaneous melanoma. J Cancer Res Clin Oncol 139:249–258

    Article  CAS  PubMed  Google Scholar 

  • Caramel J, Papadogeorgakis E, Hill L, Browne GJ, Richard G, Wierinckx A, Saldanha G, Osborne J, Hutchinson P, Tse G et al (2013) A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma. Cancer Cell 24:466–480

    Article  CAS  PubMed  Google Scholar 

  • Carlino MS, Long GV, Kefford RF, Rizos H (2015) Targeting oncogenic BRAF and aberrant MAPK activation in the treatment of cutaneous melanoma. Crit Rev Oncol Hematol 96:385–398

    Article  PubMed  Google Scholar 

  • Ceol CJ, Houvras Y, Jane-Valbuena J, Bilodeau S, Orlando DA, Battisti V, Fritsch L, Lin WM, Hollmann TJ, Ferre F et al (2011) The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature 471:513–517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheli Y, Ohanna M, Ballotti R, Bertolotto C (2010) Fifteen-year quest for microphthalmia-associated transcription factor target genes. Pigment Cell Melanoma Res 23:27–40

    Article  CAS  PubMed  Google Scholar 

  • Cheli Y, Guiliano S, Botton T, Rocchi S, Hofman V, Hofman P, Bahadoran P, Bertolotto C, Ballotti R (2011) Mitf is the key molecular switch between mouse or human melanoma initiating cells and their differentiated progeny. Oncogene 30:2307–2318

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Wang J, Shen H, Lu J, Li C, Hu D-N, Dong XD, Yan D, Tu L (2011) Epigenetics, microRNAs, and carcinogenesis: functional role of microRNA-137 in uveal melanoma. Invest Ophthalmol Vis Sci 52:1193–1199

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Wu Q, Tan L, Porter D, Jager MJ, Emery C, Bastian BC (2014) Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations. Oncogene 33:4724–4734

    Article  CAS  PubMed  Google Scholar 

  • Clemente CG, Mihm MC Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N (1996) Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77:1303–1310

    Article  CAS  PubMed  Google Scholar 

  • Conway C, Mitra A, Jewell R, Randerson-Moor J, Lobo S, Nsengimana J, Edward S, Sanders DS, Cook M, Powell B et al (2009) Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival. Am Assoc Cancer Res 15:6939–6946

    CAS  Google Scholar 

  • Conway K, Edmiston SN, Khondker ZS, Groben PA, Zhou X, Chu H, Kuan PF, Hao H, Carson C, Berwick M et al (2011) DNA-methylation profiling distinguishes malignant melanomas from benign nevi. Pigment Cell Melanoma Res 24:352–360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Criscione VD, Weinstock MA (2010) Melanoma thickness trends in the United States, 1988–2006. J Invest Dermatol 130:793–797

    Article  CAS  PubMed  Google Scholar 

  • Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho K-H, Aiba S, Bröcker E-B, LeBoit PE et al (2005) Distinct sets of genetic alterations in melanoma. N Engl J Med 353:2135–2147

    Article  CAS  PubMed  Google Scholar 

  • Curtin JA, Busam K, Pinkel D, Bastian BC (2006) Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 24:4340–4346

    Article  CAS  PubMed  Google Scholar 

  • Dahl C, Abildgaard C, Riber-Hansen R, Steiniche T, Lade-Keller J, Guldberg P (2015) KIT is a frequent target for epigenetic silencing in cutaneous melanoma. J Invest Dermatol 135:516–524

    Article  CAS  PubMed  Google Scholar 

  • Damsky W, Micevic G, Meeth K, Muthusamy V, Curley DP, Santhanakrishnan M, Erdelyi I, Platt JT, Huang L, Theodosakis N et al (2015) mTORC1 activation blocks BrafV600E-induced growth arrest but is insufficient for melanoma formation. Cancer Cell 27:41–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954

    Article  CAS  PubMed  Google Scholar 

  • Decatur CL, Ong E, Garg N et al (2016) Driver mutations in uveal melanoma: associations with gene expression profile and patient outcomes. JAMA Ophthalmol 134:728

    Article  PubMed  PubMed Central  Google Scholar 

  • Denisova E, Heidenreich B, Nagore E, Rachakonda PS, Hosen I, Akrap I, Traves V, Garcia-Casado Z, Lopez-Guerrero JA, Requena C et al (2015) Frequent DPH3 promoter mutations in skin cancers. Oncotarget 6:35922–35930

    Article  PubMed  PubMed Central  Google Scholar 

  • Dey A, Seshasayee D, Noubade R, French DM, Liu J, Chaurushiya MS, Kirkpatrick DS, Pham VC, Lill JR, Bakalarski CE et al (2012) Loss of the tumor suppressor BAP1 causes myeloid transformation. Science 337:1541–1546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dono M, Angelini G, Cecconi M, Amaro A, Esposito A, Mirisola V, Maric I, Lanza F, Nasciuti F, Viaggi S (2014) Mutation frequencies of GNAQ, GNA11, BAP1, SF3B1, EIF1AX and TERT in uveal melanoma: detection of an activating mutation in the TERT gene promoter in a single case of uveal melanoma. Br J Cancer 110:1058–1065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Draper GJ, Sanders BM, Kingston JE (1986) Second primary neoplasms in patients with retinoblastoma. Br J Cancer 53:661–671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Drobetsky EA, Turcotte J, Châteauneuf A (1995) A role for ultraviolet A in solar mutagenesis. Proc Natl Acad Sci 92:2350–2354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dutton-Regester K, Gartner JJ, Emmanuel R, Qutob N, Davies MA, Gershenwald JE, Robinson W, Robinson S, Rosenberg SA, Scolyer RA et al (2014) A highly recurrent RPS27 5'UTR mutation in melanoma. Oncotarget 5:2912–2917

    Article  PubMed  PubMed Central  Google Scholar 

  • Eberle J, Krasagakis K, Orfanos CE (1997) Translation initiation factor eIF-4A1 mRNA is consistently overexpressed in human melanoma cells in vitro. Int J Cancer 71:396–401

    Article  CAS  PubMed  Google Scholar 

  • Ehlers JP, Harbour JW (2005) NBS1 expression as a prognostic marker in uveal melanoma. Clin Cancer Res 11:1849–1853

    Article  CAS  PubMed  Google Scholar 

  • Ehlers JP, Worley L, Onken MD, Harbour JW (2005) DDEF1 is located in an amplified region of chromosome 8q and is overexpressed in uveal melanoma. Clin Cancer Res 11:3609–3613

    Article  CAS  PubMed  Google Scholar 

  • Ehlers JP, Worley L, Onken MD, Harbour JW (2008) Integrative genomic analysis of aneuploidy in uveal melanoma. Clin Cancer Res 14:115–122

    Article  CAS  PubMed  Google Scholar 

  • Emery CM, Vijayendran KG, Zipser MC, Sawyer AM, Niu L, Kim JJ, Hatton C, Chopra R, Oberholzer PA, Karpova MB et al (2009) MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci USA 106:20411–20416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Facchetti F, Previdi S, Ballarini M, Minucci S, Perego P, Porta CAML (2004) Modulation of pro- and anti-apoptotic factors in human melanoma cells exposed to histone deacetylase inhibitors. Apoptosis 9:573–582

    Article  CAS  PubMed  Google Scholar 

  • Fan T, Jiang S, Chung N, Alikhan A, Ni C, Lee CC, Hornyak TJ (2011) EZH2-dependent suppression of a cellular senescence phenotype in melanoma cells by inhibition of p21/CDKN1A expression. Mol Cancer Res 9:418–429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng X, Degese MS, Iglesias-Bartolome R, Vaque JP, Molinolo AA, Rodrigues M, Zaidi MR, Ksander BR, Merlino G, Sodhi A et al (2014) Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell 25:831–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flockhart RJ, Webster DE, Qu K, Mascarenhas N, Kovalski J, Kretz M, Khavari PA (2012) BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate melanoma cell migration. Genome Res 22:1006–1014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flørenes VA, Skrede M, Jørgensen K, Nesland JM (2004) Deacetylase inhibition in malignant melanomas: impact on cell cycle regulation and survival. Melanoma Res 14:173–181

    Article  PubMed  CAS  Google Scholar 

  • Fredriksson NJ, Ny L, Nilsson JA, Larsson E (2014) Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types. Nat Genet 46:1258–1263

    Article  CAS  PubMed  Google Scholar 

  • Furney SJ, Turajlic S, Fenwick K, Lambros MB, MacKay A, Ricken G, Mitsopoulos C, Kozarewa I, Hakas J, Zvelebil M (2012) Genomic characterisation of acral melanoma cell lines. Pigment Cell Melanoma Res 25:488–492

    Article  CAS  PubMed  Google Scholar 

  • Furney SJ, Pedersen M, Gentien D, Dumont AG, Rapinat A, Desjardins L, Turajlic S, Piperno-Neumann S, de la Grange P, Roman-Roman S (2013a) SF3B1 mutations are associated with alternative splicing in uveal melanoma. Cancer Discov 3:1122–1129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furney SJ, Turajlic S, Stamp G, Nohadani M, Carlisle A, Thomas JM, Hayes A, Strauss D, Gore M, van den Oord J (2013b) Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma. J Pathol 230:261–269

    Article  CAS  PubMed  Google Scholar 

  • Garibyan L, Fisher DE (2010) How sunlight causes melanoma. Curr Oncol Rep 12:319–326

    Article  CAS  PubMed  Google Scholar 

  • Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J (2005) Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436:117–122

    Article  CAS  PubMed  Google Scholar 

  • Gartner JJ, Parker SC, Prickett TD, Dutton-Regester K, Stitzel ML, Lin JC, Davis S, Simhadri VL, Jha S, Katagiri N (2013) Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma. Proc Natl Acad Sci 110:13481–13486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerami P, Cook RW, Russell MC, Wilkinson J, Amaria RN, Gonzalez R, Lyle S, Jackson GL, Greisinger AJ, Johnson CE et al (2015a) Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol 72:780–785.e783

    Article  CAS  PubMed  Google Scholar 

  • Gerami P, Cook RW, Wilkinson J, Russell MC, Dhillon N, Amaria RN, Gonzalez R, Lyle S, Johnson CE, Oelschlager KM et al (2015b) Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res 21:175–183

    Article  CAS  PubMed  Google Scholar 

  • Girotti MR, Saturno G, Lorigan P, Marais R (2014) No longer an untreatable disease: how targeted and immunotherapies have changed the management of melanoma patients. Mol Oncol 8:1140–1158

    Article  PubMed  PubMed Central  Google Scholar 

  • Gotea V, Gartner JJ, Qutob N, Elnitski L, Samuels Y (2015) The functional relevance of somatic synonymous mutations in melanoma and other cancers. Pigment Cell Melanoma Res 28:673–684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gschaider M, Neumann F, Peters B, Lenz F, Cibena M, Goiser M, Wolf I, Wenzel J, Mauch C, Schreiner W et al (2012) An attempt at a molecular prediction of metastasis in patients with primary cutaneous melanoma. PLoS One 7:e49865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guldberg P, thor Straten P, Birck A, Ahrenkiel V, Kirkin AF, Zeuthen J (1997) Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. Cancer Res 57:3660–3663

    CAS  PubMed  Google Scholar 

  • Haqq C, Nosrati M, Sudilovsky D, Crothers J, Khodabakhsh D, Pulliam BL, Federman S, Miller JR, Allen RE, Singer MI et al (2005) The gene expression signatures of melanoma progression. Proc Natl Acad Sci 102:6092–6097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harbour JW (2012) The genetics of uveal melanoma: an emerging framework for targeted therapy. Pigment Cell Melanoma Res 25:171–181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harbour JW, Chen R (2013) The DecisionDx-UM gene expression profile test provides risk stratification and individualized patient care in uveal melanoma. PLoS Curr 5

    Google Scholar 

  • Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA, Council ML, Matatall KA, Helms C, Bowcock AM (2010) Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330: 1410–1413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM (2013) Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat Genet 45:133–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harlin H, Meng Y, Peterson AC, Zha Y, Tretiakova M, Slingluff C, McKee M, Gajewski TF (2009) Chemokine expression in melanoma metastases associated with CD8(+) T-cell recruitment. Cancer Res 69:3077. https://doi.org/10.1158/0008-5472.CAN-1108-2281

    Article  CAS  PubMed  Google Scholar 

  • Hausler T, Stang A, Anastassiou G, Jockel KH, Mrzyk S, Horsthemke B, Lohmann DR, Zeschnigk M (2005) Loss of heterozygosity of 1p in uveal melanomas with monosomy 3. Int J Cancer 116:909–913

    Article  PubMed  CAS  Google Scholar 

  • Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat J-P, Nickerson E, Auclair D, Li L, Place C et al (2012) A landscape of driver mutations in melanoma. Cell 150:251–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, Trombetta ES (2004) Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res 64:5270–5282

    Article  CAS  PubMed  Google Scholar 

  • Hoglund M, Gisselsson D, Hansen GB, White VA, Sall T, Mitelman F, Horsman D (2004) Dissecting karyotypic patterns in malignant melanomas: temporal clustering of losses and gains in melanoma karyotypic evolution. Int J Cancer 108:57–65

    Article  PubMed  CAS  Google Scholar 

  • Hoon DSB, Spugnardi M, Kuo C, Huang SK, Morton DL, Taback B (2004) Profiling epigenetic inactivation of tumor suppressor genes in tumors and plasma from cutaneous melanoma patients. Oncogene 23:4014–4022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K et al (2013) TERT promoter mutations in familial and sporadic melanoma. Science 339:959–961

    Article  CAS  PubMed  Google Scholar 

  • Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA (2013) Highly recurrent TERT promoter mutations in human melanoma. Science 339:957–959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang JL-Y, Urtatiz O, Van Raamsdonk CD (2015) Oncogenic G protein GNAQ induces uveal melanoma and intravasation in mice. Cancer Res 75:3384–3397

    Article  CAS  PubMed  Google Scholar 

  • Hussussian CJ, Struewing JP, Goldstein AM, Higgins PAT, Ally DS, Sheahan MD, Clark WH, Tucker MA, Dracopoli NC (1994) Germline p16 mutations in familial melanoma. Nat Genet 8:15–21

    Article  CAS  PubMed  Google Scholar 

  • Hutchinson KE, Lipson D, Stephens PJ, Otto G, Lehmann BD, Lyle PL, Vnencak-Jones CL, Ross JS, Pietenpol JA, Sosman JA (2013) BRAF fusions define a distinct molecular subset of melanomas with potential sensitivity to MEK inhibition. Clin Cancer Res 19:6696–6702

    Article  CAS  PubMed  Google Scholar 

  • Hutchinson KE, Ross JS, Stephens PJ, Miller VA, Sosman JA, Pao W (2014) Melanoma BRAF fusions--response. Clin Cancer Res 20:6632

    Article  PubMed  PubMed Central  Google Scholar 

  • Jaeger J, Koczan D, Thiesen H-J, Ibrahim SM, Gross G, Spang R, Kunz M (2007) Gene expression signatures for tumor progression, tumor subtype, and tumor thickness in laser-microdissected melanoma tissues. Am Assoc Cancer Res 13:806–815

    CAS  Google Scholar 

  • Jané-Valbuena J, Widlund HR, Perner S, Johnson LA, Dibner AC, Lin WM, Baker AC, Nazarian RM, Vijayendran KG, Sellers WR et al (2010) An oncogenic role for ETV1 in melanoma. Cancer Res 70:2075–2084

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jayawardana K, Schramm S-J, Tembe V, Mueller S, Thompson JF, Scolyer RA, Mann GJ, Yang J (2016) Identification, review, and systematic cross-validation of microRNA prognostic signatures in metastatic melanoma. J Investig Dermatol 136:245–254

    Article  CAS  PubMed  Google Scholar 

  • Jensen DE, Proctor M, Marquis ST, Gardner HP, Ha SI, Chodosh LA, Ishov AM, Tommerup N, Vissing H, Sekido Y et al (1998) BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene 16:1097–1112

    Article  CAS  PubMed  Google Scholar 

  • Jin S-G, Xiong W, Wu X, Yang L, Pfeifer GP (2015) The DNA methylation landscape of human melanoma. Genomics 106:322–330

    Article  CAS  PubMed  Google Scholar 

  • Johansson P, Aoude LG, Wadt K, Glasson WJ, Warrier SK, Hewitt AW, Kiilgaard JF, Heegaard S, Isaacs T, Franchina M et al (2016) Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4. Oncotarget 7:4624–4631

    PubMed  Google Scholar 

  • Kamb A, Shattuck-Eidens D, Eeles R, Liu Q, Gruis NA, Ding W, Hussey C, Tran T, Miki Y, Weaver-Feldhaus J et al (1994) Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet 8:23–26

    Article  CAS  PubMed  Google Scholar 

  • Kampilafkos P, Melachrinou M, Kefalopoulou Z, Lakoumentas J, Sotiropoulou-Bonikou G (2015) Epigenetic modifications in cutaneous malignant melanoma: EZH2, H3K4me2, and H3K27me3 immunohistochemical expression is enhanced at the invasion front of the tumor. Am J Dermatopathol 37:138–144

    Article  PubMed  Google Scholar 

  • Kath R, Hayungs J, Bornfeld N, Sauerwein W, Höffken K, Seeber S (1993) Prognosis and treatment of disseminated uveal melanoma. Cancer 72:2219–2223

    Article  CAS  PubMed  Google Scholar 

  • Kaufman CK, Mosimann C, Fan ZP, Yang S, Thomas AJ, Ablain J, Tan JL, Fogley RD, van Rooijen E, Hagedorn EJ et al (2016) A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. Science 351 (6272) aad2197

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Khaitan D, Dinger ME, Mazar J, Crawford J, Smith MA, Mattick JS, Perera RJ (2011) The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res 71:3852–3862

    Article  CAS  PubMed  Google Scholar 

  • Kilic E, Bruggenwirth HT, Meier M, Naus NC, Beverloo HB, Meijerink JP, Luyten GP, de Klein A (2008) Increased expression of p73Deltaex2 transcript in uveal melanoma with loss of chromosome 1p. Melanoma Res 18:208–213

    Article  CAS  PubMed  Google Scholar 

  • Kim NW, Piatyszek MA, Prowse KR, Harley CB (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011

    Article  CAS  PubMed  Google Scholar 

  • Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, Cheng E, Davis MJ, Goh G, Choi M et al (2012) Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet 44:1006–1014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krauthammer M, Kong Y, Bacchiocchi A, Evans P, Pornputtapong N, Wu C, McCusker JP, Ma S, Cheng E, Straub R et al (2015) Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas. Nat Genet 47: 996–1002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Landreville S, Agapova OA, Matatall KA, Kneass ZT, Onken MD, Lee RS, Bowcock AM, Harbour JW (2012) Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. Clin Cancer Res 18:408–416

    Article  CAS  PubMed  Google Scholar 

  • Lauss M, Ringnér M, Karlsson A, Harbst K, Busch C, Geisler J, Lønning PE, Staaf J, Jönsson G (2015) DNA methylation subgroups in melanoma are associated with proliferative and immunological processes. BMC Med Genet 8:73

    Google Scholar 

  • Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA et al (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499:214–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G (2014) Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505:495–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lazova R, Pornputtapong N, Halaban R, Bosenberg M, Bai Y, Chai H, Krauthammer M (2017) Spitz nevi and Spitzoid melanomas: exome sequencing and comparison with conventional melanocytic nevi and melanomas. Mod Pathol 30:640–649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leidinger P, Keller A, Borries A, Reichrath J, Rass K, Jager SU, Lenhof H-P, Meese E (2010) High-throughput miRNA profiling of human melanoma blood samples. BMC Cancer 10:1–11

    Article  CAS  Google Scholar 

  • Leucci E, Vendramin R, Spinazzi M, Laurette P, Fiers M, Wouters J, Radaelli E, Eyckerman S, Leonelli C, Vanderheyden K et al (2016) Melanoma addiction to the long non-coding RNA SAMMSON. Nature 531:518–522

    Article  CAS  PubMed  Google Scholar 

  • Levy C, Khaled M, Fisher DE (2006) MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med 12:406–414

    Article  CAS  PubMed  Google Scholar 

  • Li M, Zhao H, Zhang X, Wood LD, Anders RA, Choti MA, Pawlik TM, Daniel HD, Kannangai R, Offerhaus GJA et al (2011) Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat Genet 43:828–829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lian CG, Xu Y, Ceol C, Wu F, Larson A, Dresser K, Xu W, Tan L, Hu Y, Zhan Q et al (2012) Loss of 5-Hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell 150:1135–1146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin WM, Baker AC, Beroukhim R, Winckler W, Feng W, Marmion JM, Laine E, Greulich H, Tseng H, Gates C et al (2008) Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res 68:664–673

    Article  CAS  PubMed  Google Scholar 

  • Linos E, Swetter SM, Cockburn MG, Colditz GA, Clarke CA (2009) Increasing burden of melanoma in the United States. J Investig Dermatol 129:1666–1674

    Article  CAS  PubMed  Google Scholar 

  • Luo L, Kessel M (2004) Geminin coordinates cell cycle and developmental control. Cell Cycle 3:709–712

    Article  Google Scholar 

  • Machida YJ, Machida Y, Vashisht AA, Wohlschlegel JA, Dutta A (2009) The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. J Biol Chem 284:34179–34188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Madonna G, Ullman CD, Gentilcore G, Palmieri G, Ascierto PA (2012) NF-kB as potential target in the treatment of melanoma. J Transl Med 10:53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maldonado JL, Fridlyand J, Patel H, Jain AN, Busam K, Kageshita T, Ono T, Albertson DG, Pinkel D, Bastian BC (2003) Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst 95:1878–1890

    Article  CAS  PubMed  Google Scholar 

  • Martin M, Maßhöfer L, Temming P, Rahmann S, Metz C, Bornfeld N, van de Nes J, Klein-Hitpass L, Hinnebusch AG, Horsthemke B (2013) Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3. Nat Genet 45:933–936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mazar J, Zhao W, Khalil AM, Lee B, Shelley J, Govindarajan SS, Yamamoto F, Ratnam M, Aftab MN, Collins S et al (2014) The functional characterization of long noncoding RNA SPRY4-IT1 in human melanoma cells. Oncotarget 5:8959–8969

    Article  PubMed  PubMed Central  Google Scholar 

  • McNulty SE, del Rosario R, Cen D, Meyskens FL Jr, Yang S (2004) Comparative expression of NFkappaB proteins in melanocytes of normal skin vs. benign intradermal naevus and human metastatic melanoma biopsies. Pigment Cell Res 17:173–180

    Article  CAS  PubMed  Google Scholar 

  • Merbs SL, Sidransky D (1999) Analysis of p16 (CDKN2/MTS-1/INK4A) alterations in primary sporadic uveal melanoma. Invest Ophthalmol Vis Sci 40:779–783

    CAS  PubMed  Google Scholar 

  • Messina JL, Fenstermacher DA, Eschrich S, Qu X, Berglund AE, Lloyd MC, Schell MJ, Sondak VK, Weber JS, Mulé JJ (2012) 12-chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy? Sci Rep 2:765

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mirzaei H, Gholamin S, Shahidsales S, Sahebkar A, Jaafari MR, Mirzaei HR, Hassanian SM, Avan A (2016) MicroRNAs as potential diagnostic and prognostic biomarkers in melanoma. Eur J Cancer 53:25–32

    Article  CAS  PubMed  Google Scholar 

  • Mitra D, Luo X, Morgan A, Wang J, Hoang MP, Lo J, Guerrero CR, Lennerz JK, Mihm MC, Wargo JA et al (2012) An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature 491:449–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mohamed A, Gonzalez RS, Lawson D, Wang J, Cohen C (2013) SOX10 expression in malignant melanoma, carcinoma, and normal tissues. Appl Immunohistochem Mol Morphol 21:506–510

    Article  CAS  PubMed  Google Scholar 

  • Moore SR, Persons DL, Sosman JA, Bobadilla D, Bedell V, Smith DD, Wolman SR, Tuthill RJ, Moon J, Sondak VK et al (2008) Detection of copy number alterations in metastatic melanoma by a DNA fluorescence in situ hybridization probe panel and array comparative genomic hybridization: a southwest oncology group study (S9431). Clin Cancer Res 14:2927–2935

    Article  CAS  PubMed  Google Scholar 

  • Moore AR, Ceraudo E, Sher JJ, Guan Y, Shoushtari AN, Chang MT, Zhang JQ, Walczak EG, Kazmi MA, Taylor BS (2016) Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma. Nat Genet 48:675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mueller DW, Rehli M, Bosserhoff AK (2009) miRNA expression profiling in melanocytes and melanoma cell lines reveals miRNAs associated with formation and progression of malignant melanoma. J Investig Dermatol 129:1740–1751

    Article  CAS  PubMed  Google Scholar 

  • Muthusamy V, Hobbs C, Nogueira C, Cordon-Cardo C, McKee PH, Chin L, Bosenberg MW (2006) Amplification of CDK4 and MDM2 in malignant melanoma. Genes Chromosom Cancer 45:447–454

    Article  CAS  PubMed  Google Scholar 

  • Nikolaev SI, Rimoldi D, Iseli C, Valsesia A, Robyr D, Gehrig C, Harshman K, Guipponi M, Bukach O, Zoete V et al (2012) Exome sequencing identifies recurrent somatic MAP 2K1 and MAP 2K2 mutations in melanoma. Nat Genet 44:133–139

    Article  CAS  Google Scholar 

  • O’Reilly KE, Warycha M, Davies MA, Rodrik V, Zhou XK, Yee H, Polsky D, Pavlick AC, Rosen N, Bhardwaj N (2009) Phosphorylated 4E-BP1 is associated with poor survival in melanoma. Clin Cancer Res 15:2872–2878

    Article  PubMed  PubMed Central  Google Scholar 

  • Onken MD, Worley LA, Ehlers JP, Harbour JW (2004) Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Cancer Res 64:7205–7209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Onken MD, Ehlers JP, Worley LA, Makita J, Yokota Y, Harbour JW (2006) Functional gene expression analysis uncovers phenotypic switch in aggressive uveal melanomas. Cancer Res 66:4602–4609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Onken MD, Worley LA, Harbour JW (2008) A metastasis modifier locus on human chromosome 8p in uveal melanoma identified by integrative genomic analysis. Clin Cancer Res 14:3737–3745

    Article  CAS  PubMed  Google Scholar 

  • Onken MD, Worley LA, Tuscan MD, Harbour JW (2010) An accurate, clinically feasible multi-gene expression assay for predicting metastasis in uveal melanoma. J Mol Diagn 12:461–468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Onken MD, Worley LA, Char DH, Augsburger JJ, Correa ZM, Nudleman E, Aaberg TM Jr, Altaweel MM, Bardenstein DS, Finger PT et al (2012) Collaborative ocular oncology group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology 119:1596–1603

    Article  PubMed  Google Scholar 

  • Ott PA, Hodi FS, Robert C (2013) CTLA-4 and PD-1/PD-L1 blockade: new immunotherapeutic modalities with durable clinical benefit in melanoma patients. Clin Cancer Res 19:5300–5309

    Article  CAS  PubMed  Google Scholar 

  • Palmer CM, Serafini DML, Schellhorn HE (1997) Near ultraviolet radiation (UVA and UVB) causes a formamidopyrimidine glycosylase-dependent increase in G to T transversions. Photochem Photobiol 65:543–549

    Article  CAS  PubMed  Google Scholar 

  • Parrella P, Sidransky D, Merbs SL (1999) Allelotype of posterior uveal melanoma: implications for a bifurcated tumor progression pathway. Cancer Res 59:3032–3037

    CAS  PubMed  Google Scholar 

  • Parrella P, Caballero OL, Sidransky D, Merbs SL (2001) Detection of c-myc amplification in uveal melanoma by fluorescent in situ hybridization. Invest Ophthalmol Vis Sci 42:1679–1684

    CAS  PubMed  Google Scholar 

  • Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pasmant E, Laurendeau I, Héron D, Vidaud M, Vidaud D, Bièche I (2007) Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res 67:3963–3969

    Article  CAS  PubMed  Google Scholar 

  • Pasmant E, Sabbagh A, Vidaud M, Bieche I (2011) ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J 25:444–448

    Article  CAS  PubMed  Google Scholar 

  • Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, Greenman CD, Varela I, Lin ML, Ordonez GR, Bignell GR et al (2010) A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 463:191–196

    Article  CAS  PubMed  Google Scholar 

  • Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J et al (2003) High frequency of BRAF mutations in nevi. Nat Genet 33:19–20

    Article  CAS  PubMed  Google Scholar 

  • Poser I, Bosserhoff AK (2004) Transcription factors involved in development and progression of malignant melanoma. Histol Histopathol 19:173–188

    CAS  PubMed  Google Scholar 

  • Poulos RC, Thoms JA, Shah A, Beck D, Pimanda JE, Wong JW (2015) Systematic screening of promoter regions pinpoints functional cis-regulatory mutations in a cutaneous melanoma genome. Mol Cancer Res 13:1218–1226

    Article  CAS  PubMed  Google Scholar 

  • Prescher G, Bornfeld N, Becher R (1990) Nonrandom chromosomal abnormalities in primary uveal melanoma. J Natl Cancer Inst 82:1765–1769

    Article  CAS  PubMed  Google Scholar 

  • Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jockel KH, Becher R (1996) Prognostic implications of monosomy 3 in uveal melanoma. Lancet 347:1222–1225

    Article  CAS  PubMed  Google Scholar 

  • Rajkumar S, Watson IR (2016) Molecular characterisation of cutaneous melanoma: creating a framework for targeted and immune therapies. Br J Cancer 115:145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rambow F, Job B, Petit V, Gesbert F, Delmas V, Seberg H, Meurice G, Van Otterloo E, Dessen P, Robert C (2015) New functional signatures for understanding melanoma biology from tumor cell lineage-specific analysis. Cell Rep 13:840–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Randerson-Moor JA, Harland M, Williams S, Cuthbert-Heavens D, Sheridan E, Aveyard J, Sibley K, Whitaker L, Knowles M, Bishop JN et al (2001) A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family. Hum Mol Genet 10:55–62

    Article  CAS  PubMed  Google Scholar 

  • Riker AI, Enkemann SA, Fodstad O, Liu S, Ren S, Morris C, Xi Y, Howell P, Metge B, Samant RS et al (2008) The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis. BMC Med Genet 1:1–16

    Google Scholar 

  • Rosenwald IB, Wang S, Savas L, Woda B, Pullman J (2003) Expression of translation initiation factor eIF-2α is increased in benign and malignant melanocytic and colonic epithelial neoplasms. Cancer 98:1080–1088

    Article  CAS  PubMed  Google Scholar 

  • Sanborn JZ, Chung J, Purdom E, Wang NJ, Kakavand H, Wilmott JS, Butler T, Thompson JF, Mann GJ, Haydu LE et al (2015) Phylogenetic analyses of melanoma reveal complex patterns of metastatic dissemination. Proc Natl Acad Sci USA 112:10995–11000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santa Cruz DJ, Hamilton PD, Klos DJ, Fernandez-Pol JA (1997) Differential expression of metallopanstimulin/S27 ribosomal protein in melanocytic lesions of the skin. J Cutan Pathol 24:533–542

    Article  CAS  PubMed  Google Scholar 

  • Sarkar D, Leung EY, Baguley BC, Finlay GJ, Askarian-Amiri ME (2015) Epigenetic regulation in human melanoma: past and future. Epigenetics 10:103–121

    Article  PubMed  PubMed Central  Google Scholar 

  • Scheuermann JC, de Ayala Alonso AG, Oktaba K, Ly-Hartig N, McGinty RK, Fraterman S, Wilm M, Muir TW, Müller J (2010) Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465:243–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Segura MF, Belitskaya-Lévy I, Rose AE, Zakrzewski J, Gaziel A, Hanniford D, Darvishian F, Berman RS, Shapiro RL, Pavlick AC et al (2010) Melanoma microRNA signature predicts post-recurrence survival. Am Assoc Cancer Res 16:1577–1586

    CAS  Google Scholar 

  • Sekiya T, Fushimi M, Hori H, Hirohashi S, Nishimura S, Sugimura T (1984) Molecular cloning and the total nucleotide sequence of the human c-Ha-ras-1 gene activated in a melanoma from a Japanese patient. Proc Natl Acad Sci 81:4771–4775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah M, Bhoumik A, Goel V, Dewing A, Breitwieser W, Kluger H, Krajewski S, Krajewska M, DeHart J, Lau E (2010) A role for ATF2 in regulating MITF and melanoma development. PLoS Genet 6:e1001258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shain AH, Bastian BC (2016) From melanocytes to melanomas. Nat Rev Cancer 16:345

    Article  CAS  PubMed  Google Scholar 

  • Shain AH, Garrido M, Botton T, Talevich E, Yeh I, Sanborn JZ, Chung J, Wang NJ, Kakavand H, Mann GJ (2015a) Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway. Nat Genet 47:1194–1199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E, Gagnon A, Dummer R, North J, Pincus L, Ruben B et al (2015b) The genetic evolution of melanoma from precursor lesions. N Engl J Med 373:1926–1936

    Article  PubMed  CAS  Google Scholar 

  • Shakhova O, Zingg D, Schaefer SM, Hari L, Civenni G, Blunschi J, Claudinot S, Okoniewski M, Beermann F, Mihic-Probst D et al (2012) Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma. Nat Cell Biol 14:882–890

    Article  CAS  PubMed  Google Scholar 

  • Sharma P, Allison JP (2015) The future of immune checkpoint therapy. Science 348:56–61

    Article  CAS  PubMed  Google Scholar 

  • Shibata T, Kokubu A, Miyamoto M, Sasajima Y, Yamazaki N (2011) Mutant IDH1 confers an in vivo growth in a melanoma cell line with BRAF mutation. Am J Pathol 178:1395–1402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shields JM, Thomas NE, Cregger M, Berger AJ, Leslie M, Torrice C, Hao H, Penland S, Arbiser J, Scott G (2007) Lack of extracellular signal-regulated kinase mitogen-activated protein kinase signaling shows a new type of melanoma. Cancer Res 67:1502–1512

    Article  CAS  PubMed  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67:7–30

    Article  PubMed  Google Scholar 

  • Sivendran S, Chang R, Pham L, Phelps RG, Harcharik ST, Hall LD, Bernardo SG, Moskalenko MM, Sivendran M, Fu Y et al (2014) Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II–III resectable disease. J Investig Dermatol 134:2202–2211

    Article  CAS  PubMed  Google Scholar 

  • Sommer L (2011) Generation of melanocytes from neural crest cells. Pigment Cell Melanoma Res 24:411–421

    Article  CAS  PubMed  Google Scholar 

  • Souroullas GP, Jeck WR, Parker JS, Simon JM, Liu JY, Paulk J, Xiong J, Clark KS, Fedoriw Y, Qi J et al (2016) An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation. Nat Med 22:632–640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stahl JM, Sharma A, Cheung M, Zimmerman M, Cheng JQ, Bosenberg MW, Kester M, Sandirasegarane L, Robertson GP (2004) Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res 64:7002–7010

    Article  CAS  PubMed  Google Scholar 

  • Straume O, Smeds J, Kumar R, Hemminki K, Akslen LA (2002) Significant impact of promoter hypermethylation and the 540 C>T polymorphism of CDKN2A in cutaneous melanoma of the vertical growth phase. Am J Pathol 161:229–237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun L, Wang Q, Gao X, Shi D, Mi S, Han Q (2015) MicroRNA-454 functions as an oncogene by regulating PTEN in uveal melanoma. FEBS Lett 589:2791–2796

    Article  CAS  PubMed  Google Scholar 

  • Talantov D, Mazumder A, Yu JX, Briggs T, Jiang Y, Backus J, Atkins D, Wang Y (2005) Novel genes associated with malignant melanoma but not benign melanocytic lesions. Clin Cancer Res 11:7234–7242

    Article  CAS  PubMed  Google Scholar 

  • Tang L, Zhang W, Su B, Yu B (2013) Long noncoding RNA HOTAIR is associated with motility, invasion, and metastatic potential of metastatic melanoma. Biomed Res Int 2013:251098

    PubMed  PubMed Central  Google Scholar 

  • Taylor JS (2015) Biomolecules. The dark side of sunlight and melanoma. Science 347:824

    Article  CAS  PubMed  Google Scholar 

  • Tembe V, Schramm S-J, Stark MS, Patrick E, Jayaswal V, Tang YH, Barbour A, Hayward NK, Thompson JF, Scolyer RA et al (2015) MicroRNA and mRNA expression profiling in metastatic melanoma reveal associations with BRAF mutation and patient prognosis. Pigment Cell Melanoma Res 28:254–266

    Article  CAS  PubMed  Google Scholar 

  • Teng DH, Hu R, Lin H, Davis T, Iliev D, Frye C, Swedlund B, Hansen KL, Vinson VL, Gumpper KL et al (1997) MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer Res 57:5221–5225

    CAS  PubMed  Google Scholar 

  • The Cancer Genome Atlas Network (2015) Genomic classification of cutaneous melanoma. Cell 161:1681–1696

    Article  PubMed Central  CAS  Google Scholar 

  • Tiffen JC, Gunatilake D, Gallagher SJ, Gowrishankar K, Heinemann A, Cullinane C, Dutton-Regester K, Pupo GM, Strbenac D, Yang JY et al (2015) Targeting activating mutations of EZH2 leads to potent cell growth inhibition in human melanoma by derepression of tumor suppressor genes. Oncotarget 6:27023–27036

    Article  PubMed  PubMed Central  Google Scholar 

  • Tirosh I, Izar B, Prakadan SM, Wadsworth MH, Treacy D, Trombetta JJ, Rotem A, Rodman C, Lian C, Murphy G et al (2016) Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352:189–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsao H, Chin L, Garraway LA, Fisher DE (2012) Melanoma: from mutations to medicine. Genes Dev 26:1131–1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tschentscher F, Husing J, Holter T, Kruse E, Dresen IG, Jockel KH, Anastassiou G, Schilling H, Bornfeld N, Horsthemke B et al (2003) Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. Cancer Res 63:2578–2584

    CAS  PubMed  Google Scholar 

  • van der Velden PA, Metzelaar-Blok JA, Bergman W, Monique H, Hurks H, Frants RR, Gruis NA, Jager MJ (2001) Promoter hypermethylation: a common cause of reduced p16(INK4a) expression in uveal melanoma. Cancer Res 61:5303–5306

    PubMed  Google Scholar 

  • Van Raamsdonk CD, Fitch KR, Fuchs H, de Angelis MH, Barsh GS (2004) Effects of G-protein mutations on skin color. Nat Genet 36:961–968

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O’Brien JM, Simpson EM, Barsh GS, Bastian BC (2009) Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457:599–602

    Article  CAS  PubMed  Google Scholar 

  • Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N (2010) Mutations in GNA11 in uveal melanoma. N Engl J Med 363:2191–2199

    Article  PubMed  PubMed Central  Google Scholar 

  • van 't Veer LJ, Burgering BM, Versteeg R, Boot AJ, Ruiter DJ, Osanto S, Schrier PI, Bos JL (1989) N-ras mutations in human cutaneous melanoma from sun-exposed body sites. Mol Cell Biol 9:3114–3116

    Article  PubMed  PubMed Central  Google Scholar 

  • Varambally S, Cao Q, Mani R-S, Shankar S, Wang X, Ateeq B, Laxman B, Cao X, Jing X, Ramnarayanan K (2008) Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322:1695–1699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wardwell-Ozgo J, Dogruluk T, Gifford A, Zhang Y, Heffernan TP, van Doorn R, Creighton CJ, Chin L, Scott KL (2014) HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome. Oncogene 33:1017–1026

    Article  CAS  PubMed  Google Scholar 

  • Watson IR, Takahashi K, Futreal PA, Chin L (2013) Emerging patterns of somatic mutations in cancer. Nat Rev Genet 14:703–718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weeraratna AT, Jiang Y, Hostetter G, Rosenblatt K, Duray P, Bittner M, Trent JM (2002) Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 1:279–288

    Article  CAS  PubMed  Google Scholar 

  • Wei X, Walia V, Lin JC, Teer JK, Prickett TD, Gartner J, Davis S, Stemke-Hale K, Davies MA, Gershenwald JE et al (2011) Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet 43:442–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weinhold N, Jacobsen A, Schultz N, Sander C, Lee W (2014) Genome-wide analysis of noncoding regulatory mutations in cancer. Nat Genet 46:1160–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weiss SA, Hanniford D, Hernando E, Osman I (2015) Revisiting determinants of prognosis in cutaneous melanoma. Cancer 121:4108–4123

    Article  PubMed  Google Scholar 

  • Whiteman DC, Watt P, Purdie DM, Hughes MC, Hayward NK, Green AC (2003) Melanocytic nevi, solar keratoses, and divergent pathways to cutaneous melanoma. J Natl Cancer Inst 95:806–812

    Article  PubMed  Google Scholar 

  • Wiesner T, Obenauf AC, Murali R, Fried I, Griewank KG, Ulz P, Windpassinger C, Wackernagel W, Loy S, Wolf I et al (2011) Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet 43:1018–1021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiesner T, He J, Yelensky R, Esteve-Puig R, Botton T, Yeh I, Lipson D, Otto G, Brennan K, Murali R et al (2014) Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat Commun 5:3116

    Article  PubMed  CAS  Google Scholar 

  • Wiesner T, Kutzner H, Cerroni L, Mihm MC, Busam KJ, Murali R (2016) Genomic aberrations in spitzoid melanocytic tumours and their implications for diagnosis, prognosis and therapy. Pathology 48:113

    Article  CAS  PubMed  Google Scholar 

  • Winnepenninckx V, Lazar V, Michiels S, Dessen P, Stas M, Alonso SR, Avril M-F, Romero PLO, Robert T, Balacescu O (2006) Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst 98:472–482

    Article  CAS  PubMed  Google Scholar 

  • Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Buschenfelde KH, Beach D (1995) A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269:1281–1284

    Article  CAS  PubMed  Google Scholar 

  • Worley LA, Long MD, Onken MD, Harbour JW (2008) Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling. Melanoma Res 18:184–190

    Article  CAS  PubMed  Google Scholar 

  • Wu C-F, Tan G-H, Ma C-C, Li L (2013) The non-coding RNA Llme23 drives the malignant property of human melanoma cells. J Genet Genomics 40:179–188

    Article  CAS  PubMed  Google Scholar 

  • Yan D, Zhou X, Chen X, Hu D-N, Dong XD, Wang J, Lu F, Tu L, Qu J (2009) MicroRNA-34a inhibits uveal melanoma cell proliferation and migration through downregulation of c-Met. Invest Ophthalmol Vis Sci 50:1559–1565

    Article  PubMed  Google Scholar 

  • Yang R, Zheng Y, Li L, Liu S, Burrows M, Wei Z, Nace A, Herlyn M, Cui R, Guo W et al (2014) Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors. Nat Commun 5:5807

    Article  CAS  PubMed  Google Scholar 

  • Yeh I, Botton T, Talevich E, Shain AH, Sparatta AJ, de la Fouchardiere A, Mully TW, North JP, Garrido MC, Gagnon A et al (2015) Activating MET kinase rearrangements in melanoma and Spitz tumours. Nat Commun 6:7174

    Article  PubMed  Google Scholar 

  • Yu F-X, Luo J, Mo J-S, Liu G, Kim YC, Meng Z, Zhao L, Peyman G, Ouyang H, Jiang W et al (2014) Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell 25:822–830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang XD, Gillespie SK, Borrow JM, Hersey P (2003) The histone deacetylase inhibitor suberic bishydroxamate: a potential sensitizer of melanoma to TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis. Biochem Pharmacol 66:1537–1545

    Article  CAS  PubMed  Google Scholar 

  • Zhang XD, Gillespie SK, Borrow JM, Hersey P (2004) The histone deacetylase inhibitor suberic bishydroxamate regulates the expression of multiple apoptotic mediators and induces mitochondria-dependent apoptosis of melanoma cells. Mol Cancer Ther 3:425–435

    Article  CAS  PubMed  Google Scholar 

  • Zingg D, Debbache J, Schaefer SM, Tuncer E, Frommel SC, Cheng P, Arenas-Ramirez N, Haeusel J, Zhang Y, Bonalli M et al (2015) The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat Commun 6:6051

    Article  CAS  PubMed  Google Scholar 

  • Zuidervaart W, van der Velden PA, Hurks MH, van Nieuwpoort FA, Out-Luiting CJ, Singh AD, Frants RR, Jager MJ, Gruis NA (2003) Gene expression profiling identifies tumour markers potentially playing a role in uveal melanoma development. Br J Cancer 89:1914–1919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zuo L, Weger J, Yang Q, Goldstein AM, Tucker MA, Walker GJ, Hayward N, Dracopoli NC (1996) Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet 12:97–99

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Rosalind and Morris Goodman Cancer Research Center, Department of Biochemistry, McGill University, Montreal, QC, Canada

    Xuan Tien Steven Nguyen & Ian R. Watson

Authors
  1. Xuan Tien Steven Nguyen
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  2. Ian R. Watson
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Corresponding author

Correspondence to Ian R. Watson .

Editor information

Editors and Affiliations

  1. Department of Dermatology, Harvard/MGH Cutaneous Biology Research Center, and Melanoma Program, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    David E. Fisher

  2. Departments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA

    Boris C. Bastian

Section Editor information

  1. Department of Dermatology, Harvard/MGH Cutaneous Biology Research Center, and Melanoma Program, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    David E. Fisher

  2. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia

    Nick Hayward

  3. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia

    David C. Whiteman

  4. Henri and Belinda Termeer Center for Targeted Therapies, MGH Cancer Center, Boston, MA, USA

    Keith T. Flaherty

  5. Framingham, MA, USA

    F. Stephen Hodi

  6. Department of Medicine, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA

    F. Stephen Hodi

  7. Auburndale, MA, USA

    Hensin Tsao

  8. Harvard-MIT Health Sciences and Technology, Cambridge, MA, USA

    Hensin Tsao

  9. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Glenn Merlino

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Nguyen, X.T.S., Watson, I.R. (2019). Melanomics: Comprehensive Molecular Analysis of Normal and Neoplastic Melanocytes. In: Fisher, D., Bastian, B. (eds) Melanoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7147-9_30

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  • DOI: https://doi.org/10.1007/978-1-4614-7147-9_30

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-7148-6

  • Online ISBN: 978-1-4614-7147-9

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