The genetics of melanoma: Recent advances

Annual Review of Genomics and Human Genetics

Volumn 14, Issue , 2013, Pages 257-279

  Hill, Victoria K ^a   Gartner, Jared J ^a   Samuels, Yardena ^a,b   Goldstein, Alisa M ^c  

^a NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^b WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Driver mutations; Germline susceptibility; High risk; Low risk; Somatic mutations

Indexed keywords

BRCA1 ASSOCIATED RING DOMAIN PROTEIN 1; CYCLIN DEPENDENT KINASE 4; CYTOSINE; MELANOCORTIN 1 RECEPTOR; MICROPHTHALMIA ASSOCIATED TRANSCRIPTION FACTOR; NUCLEOTIDE;

ATTRIBUTABLE RISK; AUTOSOMAL DOMINANT INHERITANCE; BINDING SITE; BIOINFORMATICS; BREAST CANCER; CANCER RISK; DRIVER MUTATION; EXOME; EXPOSURE; GENE; GENE LOCUS; GENE MUTATION; GENE REPLICATION; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC IDENTIFICATION; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOME; HAIR COLOR; HIGH RISK PATIENT; HUMAN; KIDNEY CANCER; MELANOGENESIS; MELANOMA; MOLECULAR BIOLOGY; NEVUS; NEXT GENERATION SEQUENCING; NONHUMAN; NUCLEOTIDE SEQUENCE; PANCREAS CANCER; PATHOGENESIS; PHENOTYPE; PIGMENTATION; PREVALENCE; REVIEW; SAMPLE SIZE; SINGLE NUCLEOTIDE POLYMORPHISM; SOMATIC MUTATION; TUMOR SUPPRESSOR GENE; ULTRAVIOLET RADIATION; VERTICAL TRANSMISSION;

GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MELANOMA; MUTATION; SKIN NEOPLASMS;

EID: 84884293805     PISSN: 15278204     EISSN: 1545293X     Source Type: Book Series    
DOI: 10.1146/annurev-genom-091212-153429     Document Type: Review

References (153)

1. Abdel-Rahman MH, Pilarski R, Cebulla CM, Massengill JB, Christopher BN, et al. 2011. Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. J. Med. Genet. 48:856-59
2. Aitken J, Welch J, Duffy D, Milligan A, Green A, et al. 1999. CDKN2A variants in a population-based sample of Queensland families with melanoma. J. Natl. Cancer Inst. 91:446-52
3. Amos CI, Wang LE, Lee JE, Gershenwald JE, Chen WV, et al. 2011. Genome-wide association study identifies novel loci predisposing to cutaneous melanoma. Hum. Mol. Genet. 20:5012-23
4. Apte SS. 2004. A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motifs: The ADAMTS family. Int. J. Biochem. Cell Biol. 36:981-85
5. Bale SJ, DracopoliNC, Tucker MA, ClarkWH Jr, Fraser MC, et al. 1989. Mapping the gene for hereditary cutaneous malignant melanoma-Dysplastic nevus to chromosome 1p. N. Engl. J.Med. 320:1367-72
6. Barrett JH, Iles MM, Harland M, Taylor JC, Aitken JF, et al. 2011. Genome-wide association study identifies three new melanoma susceptibility loci. Nat. Genet. 43:1108-13
7. Begg CB, Orlow I, Hummer AJ, Armstrong BK, Kricker A, et al. 2005. Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. J. Natl. Cancer Inst. 97:1507-15
8. Berger MF, Garraway LA. 2009. Applications of genomics in melanoma oncogene discovery. Hematol. Oncol. Clin. N. Am. 23:397-414
9. Berger MF, Hodis E, Heffernan TP, Deribe YL, LawrenceMS, et al. 2012. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 485:502-6
10. BergmanW, Gruis N. 1996. Familial melanoma and pancreatic cancer. N. Engl. J. Med. 334:471-72
11. Bertolotto C, Lesueur F, Giuliano S, Strub T, De LichyM, et al. 2011. A SUMOylation-DefectiveMITF germline mutation predisposes to melanoma and renal carcinoma. Nature 480:94-98
12. Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, et al. 2011. Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science 333:1453-55
13. Bishop DT, Demenais F, Goldstein AM, BergmanW, Bishop JN, et al. 2002. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J. Natl. Cancer Inst. 94:894-903
14. Bishop DT, Demenais F, Iles MM, Harland M, Taylor JC, et al. 2009. Genome-wide association study identifies three loci associated with melanoma risk. Nat. Genet. 41:920-25
15. Borg A, Sandberg T, Nilsson K, Johannsson O, Klinker M, et al. 2000. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J. Natl. Cancer Inst. 92:1260-66
16. Brown KM, MacGregor S, Montgomery GW, Craig DW, Zhao ZZ, et al. 2008. Common sequence variants on 20q11.22 confer melanoma susceptibility. Nat. Genet. 40:838-40
17. Busca R, Ballotti R. 2000. Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res. 13:60-69
18. Cancer Genome Atlas Res. Netw. 2011. Integrated genomic analyses of ovarian carcinoma. Nature 474:609-15
19. Cannon-Albright LA, Teerlink CC, Farnham JM, Thomas AW, Zone JJ, Leachman SA. 2013. Linkage analysis of extended high-risk pedigrees replicates a cutaneous malignant melanoma predisposition locus on chromosome 9q21. J. Investig. Dermatol. 133:128-34
20. Carbone M, Ferris LK, Baumann F, Napolitano A, Lum CA, et al. 2012. BAP1 cancer syndrome: Malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. J. Transl. Med. 10:179
21. Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, et al. 2007. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 448:439-44
22. Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, et al. 2011. KIT as a therapeutic target in metastatic melanoma. JAMA 305:2327-34
23. Chatzinasiou F, Lill CM, Kypreou K, Stefanaki I, Nicolaou V, et al. 2011. Comprehensive field synopsis and systematic meta-Analyses of genetic association studies in cutaneous melanoma. J. Natl. Cancer Inst. 103:1227-35
24. Chaudru V, Chompret A, Bressac-De Paillerets B, Spatz A, Avril MF, Demenais F. 2004. Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families. J. Natl. Cancer Inst. 96:785-95
25. Chaudru V, Laud K, Avril MF, Miniere A, Chompret A, et al. 2005. Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees. Cancer Epidemiol. Biomark. Prev. 14:2384-90
26. 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
27. Choi KY, Chang K, Pickel JM, Badger JD 2nd, Roche KW. 2011. Expression of the metabotropic glutamate receptor 5 (mGluR5) induces melanoma in transgenicmice. Proc.Natl. Acad. Sci. USA108:15219-24
28. Cronin JC, Wunderlich J, Loftus SK, Prickett TD, Wei X, et al. 2009. Frequent mutations in the MITF pathway in melanoma. Pigment Cell Melanoma Res. 22:435-44
29. Cruz F III, Rubin BP, Wilson D, Town A, Schroeder A, et al. 2003. Absence of BRAF and NRAS mutations in uveal melanoma. Cancer Res. 63:5761-66
30. Curtin JA, Busam K, Pinkel D, Bastian BC. 2006. Somatic activation of KIT in distinct subtypes of melanoma. J. Clin. Oncol. 24:4340-46
31. Curtin JA, Fridlyand J, Kageshita T, PatelHN, Busam KJ, et al. 2005. Distinct sets of genetic alterations in melanoma. N. Engl. J. Med. 353:2135-47
32. Cust AE, Harland M, Makalic E, Schmidt D, Dowty JG, et al. 2011. Melanoma risk for CDKN2A mutation carriers who are relatives of population-based case carriers in Australia and the UK. J. Med. Genet. 48:266-72
33. Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, et al. 2010. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 463:360-63
34. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, et al. 2002. Mutations of the BRAF gene in human cancer. Nature 417:949-54
35. Davies MA, Stemke-Hale K, Tellez C, Calderone TL, Deng W, et al. 2008. A novel AKT3 mutation in melanoma tumours and cell lines. Br. J. Cancer 99:1265-68
36. Debniak T, Jakubowska A, Serrano-Fernández P, Kurzawski G, Cybulski C, et al. 2011. Association of MMP8 gene variation with an increased risk of malignant melanoma. Melanoma Res. 21:464-68
37. Demenais F, Mohamdi H, Chaudru V, Goldstein AM, Newton Bishop JA, et al. 2010. Association of MC1R variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: A GenoMEL study. J. Natl. Cancer Inst. 102:1568-83
38. De Snoo FA, Bishop DT, Bergman W, van Leeuwen I, Van Der Drift C, et al. 2008. Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma families. Clin. Cancer Res. 14:7151-57
39. Duffy DL, Zhao ZZ, Sturm RA, Hayward NK, Martin NG, Montgomery GW. 2010. Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma. J. Investig. Dermatol. 130:520-28
40. Falchi M, Bataille V, Hayward NK, Duffy DL, Bishop JA, et al. 2009. Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi. Nat. Genet. 41:915-19
41. Fecher LA, Cummings SD, KeefeMJ, Alani RM. 2007. Toward a molecular classification of melanoma. J. Clin. Oncol. 25:1606-20
42. FernandezLP, MilneRL, Pita G, Avilés JA, LázaroP, et al. 2008. SLC45A2: A novel malignant melanomaassociated gene. Hum. Mutat. 29:1161-67
43. Flaherty KT. 2011. BRAF inhibitors and melanoma. Cancer J. 17:505-11
44. Flanagan N, Healy E, Ray A, Philips S, Todd C, et al. 2000. Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation. Hum. Mol. Genet. 9:2531-37
45. Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, et al. 2005. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436:117-22
46. Gerstenblith MR, Goldstein AM, Fargnoli MC, Peris K, Landi MT. 2007. Comprehensive evaluation of allele frequency differences of MC1R variants across populations. Hum. Mutat. 28:495-505
47. Gerstenblith MR, Shi J, Landi MT. 2010. Genome-wide association studies of pigmentation and skin cancer: A review and meta-Analysis. Pigment Cell Melanoma Res. 23:587-606
48. Gillanders E, Juo SH, Holland EA, JonesM, NancarrowD, et al. 2003. Localization of a novel melanoma susceptibility locus to 1p22. Am. J. Hum. Genet. 73:301-13
49. Goldstein AM, Chan M, Harland M, Gillanders EM, Hayward NK, et al. 2006. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uvealmelanoma acrossGenoMEL. Cancer Res. 66:9818-28
50. Goldstein AM, Chan M, Harland M, Hayward NK, Demenais F, et al. 2007. Features associated with germline CDKN2A mutations: A GenoMEL study of melanoma-prone families from three continents. J. Med. Genet. 44:99-106
51. Goldstein AM, Falk RT, FraserMC, Dracopoli NC, Sikorski RS, et al. 1998. Sun-related risk factors in melanoma-prone families with CDKN2A mutations. J. Natl. Cancer Inst. 90:709-11
52. Goldstein AM, Fraser MC, Struewing JP, Hussussian CJ, Ranade K, et al. 1995. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N. Engl. J. Med. 333:970-74
53. Goldstein AM, Stacey SN, Olafsson JH, Jonsson GF, Helgason A, et al. 2008. CDKN2A mutations and melanoma risk in the Icelandic population. J. Med. Genet. 45:284-89
54. Goldstein AM, Struewing JP, Fraser MC, Smith MW, Tucker MA. 2004. Prospective risk of cancer in CDKN2A germline mutation carriers. J. Med. Genet. 41:421-24
55. Goldstein AM, Tucker MA. 2001. Genetic epidemiology of cutaneous melanoma: A global perspective. Arch. Dermatol. 137:1493-96
56. Goydos JS, MannB, Kim HJ, Gabriel EM, Alsina J, et al. 2005. Detection of B-RAF and N-RAS mutations in human melanoma. J. Am. Coll. Surg. 200:362-70
57. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, et al. 2007. Patterns of somatic mutation in human cancer genomes. Nature 446:153-58
58. Grichnik JM. 2006. Kit and melanocyte migration. J. Investig. Dermatol. 126:945-47
59. Gudbjartsson DF, Sulem P, Stacey SN, Goldstein AM, Rafnar T, et al. 2008. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma. Nat. Genet. 40:886-91
60. GuedjM, BourillonA, Combadieres C, RoderoM, Dieude P, et al. 2008. Variants of theMATP/SLC45A2 gene are protective for melanoma in the French population. Hum. Mutat. 29:1154-60
61. Guo J, Si L, Kong Y, Flaherty KT, Xu X, et al. 2011. Phase II, open-label, single-Arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J. Clin. Oncol. 29:2904-9
62. Haluska FG, Tsao H, Wu H, Haluska FS, Lazar A, Goel V. 2006. Genetic alterations in signaling pathways in melanoma. Clin. Cancer Res. 12:2301s-7s
63. Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, et al. 2010. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330:1410-13
64. Hayward NK. 2003. Genetics of melanoma predisposition. Oncogene 22:3053-62
65. Helsing P, Nymoen DA, Ariansen S, Steine SJ, Maehle L, et al. 2008. Population-based prevalence of CDKN2A and CDK4 mutations in patients with multiple primary melanomas. Genes Chromosomes Cancer 47:175-84
66. Hocker T, Tsao H. 2007. Ultraviolet radiation and melanoma: A systematic review and analysis of reported sequence variants. Hum. Mutat. 28:578-88
67. Hodis E, Watson IR, Kryukov GV, Arold ST, ImielinskiM, et al. 2012. A landscape of driver mutations in melanoma. Cell 150:251-63
68. Hou L, Pavan WJ. 2008. Transcriptional and signaling regulation in neural crest stem cell-Derived melanocyte development: Do all roads lead to Mitf? Cell Res. 18:1163-76
69. Jannot AS, Meziani R, Bertrand G, Gerard B, Descamps V, et al. 2005. Allele variations in the OCA2 gene (pink-eyed-Dilution locus) are associated with genetic susceptibility to melanoma. Eur. J. Hum. Genet. 13:913-20
70. Jiao Y, Shi C, Edil BH, De Wilde RF, Klimstra DS, et al. 2011. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331:1199-203
71. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, et al. 2008. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321:1801-6
72. Jonsson G, Bendahl PO, Sandberg T, Kurbasic A, Staaf J, et al. 2005. Mapping of a novel ocular and cutaneous malignant melanoma susceptibility locus to chromosome 9q21.32. J. Natl. Cancer Inst. 97:1377-82
73. Kanetsky PA, Panossian S, Elder DE, Guerry D, Ming ME, et al. 2010. Does MC1R genotype convey information about melanoma risk beyond risk phenotypes? Cancer 116:2416-28
74. Kanetsky PA, Rebbeck TR, Hummer AJ, Panossian S, Armstrong BK, et al. 2006. Population-based study of natural variation in the melanocortin-1 receptor gene and melanoma. Cancer Res. 66:9330-37
75. Kanetsky PA, Swoyer J, Panossian S, Holmes R, Guerry D, Rebbeck TR. 2002. A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Am. J. Hum. Genet. 70:770-75
76. Kolch W. 2005. Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat. Rev. Mol. Cell Biol. 6:827-37
77. Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, et al. 2012. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat. Genet. 44:1006-14
78. Kumar R, Angelini S, Czene K, Sauroja I, Hahka-Kemppinen M, et al. 2003. BRAF mutations in metastatic melanoma: A possible association with clinical outcome. Clin. Cancer Res. 9:3362-68
79. Kumar R, Angelini S, Snellman E, Hemminki K. 2004. BRAF mutations are common somatic events in melanocytic nevi. J. Investig. Dermatol. 122:342-48
80. Law MH, MacGregor S, Hayward NK. 2012. Melanoma genetics: Recent findings take us beyond welltraveled pathways. J. Investig. Dermatol. 132:1763-74
81. Law MH, Montgomery GW, Brown KM, Martin NG, Mann GJ, et al. 2012. Meta-Analysis combining new and existing data sets confirms that the TERT-CLPTM1L locus influences melanoma risk. J. Investig. Dermatol. 132:485-87
82. Lee W, Jiang Z, Liu J, Haverty PM, Guan Y, et al. 2010. The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature 465:473-77
83. Li M, Zhao H, Zhang X, Wood LD, Anders RA, et al. 2011. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat. Genet. 43:828-29
84. LinWM, Baker AC, Beroukhim R, WincklerW, FengW, et al. 2008. Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res. 68:664-73
85. Maccioni L, Rachakonda PS, Scherer D, Bermejo JL, Planelles D, et al. 2012. Variants at chromosome 20 (ASIP locus) and melanoma risk. Int. J. Cancer 132:42-65
86. MacGregor S, Montgomery GW, Liu JZ, Zhao ZZ, Henders AK, et al. 2011. Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3. Nat. Genet. 43:1114-18
87. Mangana J, Levesque MP, KarpovaMB, DrummerR. 2012. Sorafenib inmelanoma. Expert Opin. Investig. Drugs 21:557-68
88. Mochizuki S, Okada Y. 2007. ADAMs in cancer cell proliferation and progression. Cancer Sci. 98:621-28
89. Molven A, GrimstvedtMB, Steine SJ, HarlandM, Avril MF, et al. 2005. A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation. Genes Chromosomes Cancer 44:10-18
90. Monsel G, Ortonne N, Bagot M, Bensussan A, Dumaz N. 2009. c-Kitmutants require hypoxia-inducible factor 1ato transform melanocytes. Oncogene 29:227-36
91. Nan H, Kraft P, Hunter DJ, Han J. 2009. Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians. Int. J. Cancer 125:909-17
92. Nikolaev SI, Rimoldi D, Iseli C, Valsesia A, Robyr D, et al. 2012. Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma. Nat. Genet. 44:133-39
93. Nikolaou V, Kang X, Stratigos A, GogasH, Latorre MC, et al. 2011. Comprehensivemutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma. Br. J. Dermatol. 165:1219-22
94. Njauw CN, Kim I, Piris A, Gabree M, Taylor M, et al. 2012. Germline BAP1 inactivation is preferentially associated with metastatic ocular melanoma and cutaneous-ocular melanoma families. PLoS ONE 7:e35295
95. Olson MF, Marais R. 2000. Ras protein signalling. Semin. Immunol. 12:63-73
96. Omholt K, Karsberg S, Platz A, Kanter L, Ringborg U, Hansson J. 2002. Screening of N-ras codon 61 mutations in paired primary and metastatic cutaneous melanomas: Mutations occur early and persist throughout tumor progression. Clin. Cancer Res. 8:3468-74
97. Omholt K, Platz A, Kanter L, Ringborg U, Hansson J. 2003. NRASandBRAFmutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Clin. Cancer Res. 9:6483-88
98. Orlow I, Begg CB, Cotignola J, Roy P, Hummer AJ, et al. 2007. CDKN2A germline mutations in individuals with cutaneous malignant melanoma. J. Investig. Dermatol. 127:1234-43
99. Padua RA, Barrass NC, Currie GA. 1985. Activation of N-ras in a human melanoma cell line. Mol. Cell. Biol. 5:582-85
100. Palavalli LH, Prickett TD, Wunderlich JR, Wei X, Burrell AS, et al. 2009. Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma. Nat. Genet. 41:518-20
101. Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, et al. 2011. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N. Engl. J. Med. 365:1384-95
102. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, et al. 2008. An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807-12
103. Parsons DW, Li M, Zhang X, Jones S, Leary RJ, et al. 2011. The genetic landscape of the childhood cancer medulloblastoma. Science 331:435-39
104. Pastorino L, Cusano R, Bruno W, Lantieri F, Origone P, et al. 2004. Novel MC1R variants in Ligurian melanoma patients and controls. Hum. Mutat. 24:103
105. Peric B, Cerkovnik P, Novakovic S, Zgajnar J, Besic N, Hocevar M. 2008. Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families. BMC Med. Genet. 9:86
106. Pjanova D, Engele L, Randerson-Moor JA, Harland M, Bishop DT, et al. 2007. CDKN2A and CDK4 variants in Latvian melanoma patients: Analysis of a clinic-based population. Melanoma Res. 17:185-91
107. Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, et al. 2010. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 463:191-96
108. Pollock PM, Cohen-Solal K, Sood R, Namkoong J, Martino JJ, et al. 2003. Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Nat. Genet. 34:108-12
109. Pollock PM, HarperU L, Hansen KS, Yudt LM, Stark M, et al. 2003. High frequency of BRAF mutations in nevi. Nat. Genet. 33:19-20
110. Pomerantz J, Schreiber-Agus N, Liegeois NJ, Silverman A, Alland L, et al. 1998. The Ink4a tumor suppressor gene produc t, p19Arf , interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell 92:713-23
111. Prickett TD, Agrawal NS, Wei X, Yates KE, Lin JC, et al. 2009. Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat. Genet. 41:1127-32
112. Prickett TD, Samuels Y. 2012. Molecular pathways: Dysregulated glutamatergic signaling pathways in cancer. Clin. Cancer Res. 18:4240-46
113. Prickett TD, Wei X, Cardenas-Navia I, Teer JK, Lin JC, et al. 2011. Exon capture analysis ofGproteincoupled receptors identifies activating mutations in GRM3 in melanoma. Nat. Genet. 43:1119-26
114. Puntervoll HE, Yang XR, Vetti HH, Bachmann IM, Avril MF, et al. 2013. Melanoma prone families with CDK4 germline mutation: Phenotypic profile and association with MC1R variants. J. Med. Genet. 50:264-70
115. Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, et al. 2009. Sequence variants at the TERTCLPTM1L locus associate with many cancer types. Nat. Genet. 41:221-27
116. Raimondi S, Sera F, Gandini S, Iodice S, Caini S, et al. 2008. MC1R variant s, melanoma and red hair color phenotype: A meta-Analysis. Int. J. Cancer 122:2753-60
117. Rees JL. 2004. The genetics of sun sensitivity in humans. Am. J. Hum. Genet. 75:739-51
118. Serrano M, Gomez-Lahoz E, DePinho RA, Beach D, Bar-Sagi D. 1995. Inhibition of ras-induced proliferation and cellular transformation by p16INK4. Science 267:249-52
119. Serrano M, Hannon GJ, Beach D. 1993. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366:704-7
120. Shin SS, Namkoong J, Wall BA, Gleason R, LeeH J, Chen S. 2008. Oncogenic activities ofmetabotropic glutamate receptor 1 (Grm1) in melanocyte transformation. Pigment Cell Melanoma Res. 21:368-78
121. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, et al. 2006. The consensus coding sequences of human breast and colorectal cancers. Science 314:268-74
122. Solomon DA, Kim JS, Cronin JC, Sibenaller Z, Ryken T, et al. 2008. Mutational inactivation of PTPRD in glioblastoma multiforme and malignant melanoma. Cancer Res. 68:10300-6
123. Song MS, Salmena L, Pandolfi PP. 2012. The functions and regulation of the PTEN tumour suppressor. Nat. Rev. Mol. Cell Biol. 13:283-96
124. Soufir N, Avril MF, Chompret A, Demenais F, Bombled J, et al. 1998. Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. Hum. Mol. Genet. 7:209-16
125. Stacey SN, Sulem P, Masson G, Gudjonsson SA, Thorleifsson G, et al. 2009. New common variants affecting susceptibility to basal cell carcinoma. Nat. Genet. 41:909-14
126. Stahl JM, Sharma A, Cheung M, Zimmerman M, Cheng JQ, et al. 2004. Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res. 64:7002-10
127. Stark MS, Woods SL, Gartside MG, Bonazzi VF, Dutton-Regester K, et al. 2011. Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing. Nat. Genet. 44:165-69
128. Sturm RA, Duffy DL, Box NF, Chen W, Smit DJ, et al. 2003. The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes. Pigment Cell Res. 16:266-72
129. Teerlink C, Farnham J, Allen-Brady K, Camp NJ, Thomas A, et al. 2012. A unique genome-wide association analysis in extended Utah high-risk pedigrees identifies a novel melanoma risk variant on chromosome arm 10q. Hum. Genet. 131:77-85
130. Testa JR, Cheung M, Pei J, Below JE, Tan Y, et al. 2011. Germline BAP1 mutations predispose to malignant mesothelioma. Nat. Genet. 43:1022-25
131. Tsao H, Mihm MC Jr, Sheehan C. 2003. PTEN expression in normal ski n, acquired melanocytic nev i, and cutaneous melanoma. J. Am. Acad. Dermatol. 49:865-72
132. Tsao H, Zhang X, Benoit E, Haluska FG. 1998. Identification ofPTEN/MMACIalterations in uncultured melanomas and melanoma cell lines. Oncogene 16:3397-402
133. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, et al. 2009. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457:599-602
134. Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, et al. 2010. Mutations in GNA11 in uveal melanoma. N. Engl. J. Med. 363:2191-99
135. van't Veer LJ, Burgering BM, Versteeg R, Boot AJ, Ruiter DJ, et al. 1989. N-ras mutations in human cutaneous melanoma from sun-exposed body sites. Mol. Cell. Biol. 9:3114-16
136. Varela I, Tarpey P, Raine K, Huang D, Ong CK, et al. 2011. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469:539-42
137. Viloria CG, Obaya AJ, Moncada-Pazos A, Llamazares M, Astudillo A, et al. 2009. Genetic inactivation of ADAMTS15 metalloprotease in human colorectal cancer. Cancer Res. 69:4926-34
138. Wadt K, Choi J, Chung JY, Kiilgaard J, Heegaard S, et al. 2012. A cryptic BAP1 splice mutation in a family with uveal and cutaneous melanom a, and paraganglioma. Pigment Cell Melanoma Res. 25:815-18
139. Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, et al. 2011. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J. Clin. Oncol. 29:3085-96
140. Walia V, Mu EW, Lin JC, Samuels Y. 2012. Delving into somatic variation in sporadic melanoma. Pigment Cell Melanoma Res. 25:155-70
141. Wei X, Moncada-Pazos A, Cal S, Soria-Valles C, Gartner J, et al. 2011. Analysis of the disintegrinmetalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma. Hum. Mutat. 32:E2148-75
142. Wei X, Prickett TD, Viloria CG, Molinolo A, Lin JC, et al. 2010. Mutational and functional analysis reveals ADAMTS18 metalloproteinase as a novel driver in melanoma. Mol. Cancer Res. 8:1513-25
143. Wei X, Walia V, Lin JC, Teer JK, Prickett TD, et al. 2011. Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat. Genet. 43:442-46
144. Wiesner T, Fried I, Ulz P, Stacher E, Popper H, et al. 2012. Toward an improved definition of the tumor spectrum associated with BAP1 germline mutations. J. Clin. Oncol. 30:e337-40
145. Wiesner T, Obenauf AC, Murali R, Fried I, Griewank KG, et al. 2011. Germline mutations in BAP1 predispose to melanocytic tumors. Nat. Genet. 43:1018-21
146. Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, et al. 1995. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269:1281-84
147. Wong TH, Rees JL. 2005. The relation between melanocortin 1 receptor (MC1R) variation and the generation of phenotypic diversity in the cutaneous response to ultraviolet radiation. Peptides 26:1965-71
148. Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, et al. 2007. The genomic landscapes of human breast and colorectal cancers. Science 318:1108-13
149. Wu H, Goel V, Haluska FG. 2003. PTEN signaling pathways in melanoma. Oncogene 22:3113-22
150. Yokoyama S, Woods SL, Boyle GM, AouDe LG, MacGregor S, et al. 2011. A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature 480:99-103
151. Zhang M, Qureshi AA, Guo Q, Han J. 2011. Genetic variation in DNA repair pathway genes and melanoma risk. DNA Repair 10:111-16
152. Zhang Y, Xiong Y, Yarbrough WG. 1998. ARF promotesMDM2 degradation and stabilizes p53: ARFINK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92:725-34
153. Zuo L, Weger J, Yang Q, Goldstein AM, Tucker MA, et al. 1996. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat. Genet. 12:97-99