Abstract
There have been major advances in our understanding of the molecular epidemiology of melanoma over the past decade. Comprehensive cataloguing of a landscape of driver mutations has enabled identification of the key pathways that underscore the biological processes and therapeutic opportunities in melanoma. This new knowledge has been complemented by an improved understanding of the genetic susceptibility of melanoma, in pigmentation, nevus, telomere, and other biological pathways, identified mainly by genome-wide association studies. This chapter describes the genetic basis for melanoma, including cutaneous melanoma of non-desmoplastic and desmoplastic types, acral, mucosal, and uveal melanomas. It describes analyses of gene-environment, gene-gene (epistasis), and gene-phenotype interactions that have led to an improved understanding of the biological processes involved in melanoma development and more accurate prediction of an individual’s melanoma risk. The research presented highlights the exciting developments that have come from combining different types of data, including somatic, germline, clinical, pathologic, phenotypic, and environmental risk factors.
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References
Abdel-Rahman MH et al (2011) Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. J Med Genet 48: 856–859. https://doi.org/10.1136/jmedgenet-2011-100156
Aitken JF, Bailey-Wilson J, Green AC, MacLennan R, Martin NG (1998) Segregation analysis of cutaneous melanoma in Queensland. Genet Epidemiol 15: 391–401. https://doi.org/10.1002/(SICI)1098-2272(1998)15:4<391::AID-GEPI5>3.0.CO;2-5
Amos CI et al (2011) Genome-wide association study identifies novel loci predisposing to cutaneous melanoma. Hum Mol Genet 20:5012–5023. https://doi.org/10.1093/hmg/ddr415
Aoude LG, Wadt KA, Pritchard AL, Hayward NK (2015a) Genetics of familial melanoma: 20 years after CDKN2A. Pigment Cell Melanoma Res 28:148–160. https://doi.org/10.1111/pcmr.12333
Aoude LG et al (2015b) Nonsense mutations in the shelterin complex genes ACD and TERF2IP in familial melanoma. J Natl Cancer Inst 107. https://doi.org/10.1093/jnci/dju408
Armstrong BK, Cust AE (2017) Sun exposure and skin cancer, and the puzzle of cutaneous melanoma: a perspective on fears et al. mathematical models of age and ultraviolet effects on the incidence of skin cancer among whites in the United States. Am J Epidemiol 1977 105:420–427. Cancer Epidemiol 48:147–156. https://doi.org/10.1016/j.canep.2017.04.004
Bai X et al (2017) MAPK pathway and TERT promoter gene mutation pattern and its prognostic value in melanoma patients: a retrospective study of 2,793 cases. Clin Cancer Res 23:6120–6127. https://doi.org/10.1158/1078-0432.CCR-17-0980
Barrett JH et al (2011) Genome-wide association study identifies three new melanoma susceptibility loci. Nat Genet 43:1108–1113. https://doi.org/10.1038/ng.959
Barrett JH et al (2015) Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions. Int J Cancer 136:1351–1360. https://doi.org/10.1002/ijc.29099
Bataille V et al (2007) Nevus size and number are associated with telomere length and represent potential markers of a decreased senescence in vivo. Cancer Epidemiol Biomark Prev 16:1499–1502. https://doi.org/10.1158/1055-9965.EPI-07-0152
Bauer J, Curtin JA, Pinkel D, Bastian BC (2007) Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol 127:179–182
Begg CB et al (2004) Familial aggregation of melanoma risks in a large population-based sample of melanoma cases. Cancer Causes Control 15:957–965. https://doi.org/10.1007/s10522-004-2474-2
Begg CB et al (2005) Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. J Natl Cancer Inst 97:1507–1515. https://doi.org/10.1093/jnci/dji312
Berwick M et al (2014) MITF E318K’s effect on melanoma risk independent of, but modified by, other risk factors. Pigment Cell Melanoma Res 27:485–488. https://doi.org/10.1111/pcmr.12215
Bishop DT et al (2002) Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst 94:894–903
Bishop DT et al (2009) Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet 41:920–925. https://doi.org/10.1038/ng.411
Brossard M et al (2015) Integrated pathway and epistasis analysis reveals interactive effect of genetic variants at TERF1 and AFAP1L2 loci on melanoma risk. Int J Cancer 137:1901–1909. https://doi.org/10.1002/ijc.29570
Brown KM et al (2008) Common sequence variants on 20q11.22 confer melanoma susceptibility. Nat Genet 40:838–840. https://doi.org/10.1038/ng.163
Cancer Genome Atlas N (2015) Genomic classification of cutaneous melanoma. Cell 161:1681–1696. https://doi.org/10.1016/j.cell.2015.05.044
Cannon-Albright LA et al (1992) Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22. Science 258:1148–1152
Carbone M et al (2012) BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. J Transl Med 10:179. https://doi.org/10.1186/1479-5876-10-179
Cawley EP, Kruse WT, Pinkus HK (1952) Genetic aspects of malignant melanoma. AMA Arch Derm Syphilol 65:440–450
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 96:785–795
Cirenajwis H et al (2017) NF1-mutated melanoma tumors harbor distinct clinical and biological characteristics. Mol Oncol 11:438–451. https://doi.org/10.1002/1878-0261.12050
Codd V et al (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet 45(422–427):427e421–427e422. https://doi.org/10.1038/ng.2528
Cole BS, Hall MA, Urbanowicz RJ, Gilbert-Diamond D, Moore JH (2017) Analysis of gene-gene interactions. Curr Protoc Hum Genet 95:1 14 11–11 14 10. https://doi.org/10.1002/cphg.45
Cowan JM, Halaban R, Francke U (1988) Cytogenetic analysis of melanocytes from premalignant nevi and melanomas. J Natl Cancer Inst 80:1159–1164
Cust AE 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: 266–272. https://doi.org/10.1136/jmg.2010.086538
Cust AE et al (2012) MC1R genotypes and risk of melanoma before age 40 years: a population-based case-control-family study. Int J Cancer 131:E269–E281. https://doi.org/10.1002/ijc.27357
Cust AE et al (2018) Assessing the incremental contribution of common genomic variants to melanoma risk prediction in two population-based studies. J Invest Dermatol 138:2617. https://doi.org/10.1016/j.jid.2018.05.023
de Snoo FA, Hayward NK (2005) Cutaneous melanoma susceptibility and progression genes. Cancer Lett 230:153–186. https://doi.org/10.1016/j.canlet.2004.12.033
Demenais F et al (2010) Association of MC1R variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study. J Natl Cancer Inst 102:1568–1583. https://doi.org/10.1093/jnci/djq363
Dudbridge F (2013) Power and predictive accuracy of polygenic risk scores. PLoS Genet 9:e1003348. https://doi.org/10.1371/journal.pgen.1003348
Dudbridge F, Fletcher O (2014) Gene-environment dependence creates spurious gene-environment interaction. Am J Hum Genet 95:301–307. https://doi.org/10.1016/j.ajhg.2014.07.014
Duffy DL et al (2004) Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Hum Mol Genet 13:447–461. https://doi.org/10.1093/hmg/ddh043
Duffy DL, Zhao ZZ, Sturm RA, Hayward NK, Martin NG, Montgomery GW (2010a) Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma. J Invest Dermatol 130:520–528. https://doi.org/10.1038/jid.2009.258
Duffy DL et al (2010b) IRF4 variants have age-specific effects on nevus count and predispose to melanoma. Am J Hum Genet 87:6–16. https://doi.org/10.1016/j.ajhg.2010.05.017
Ellerhorst JA et al (2011) Clinical correlates of NRAS and BRAF mutations in primary human melanoma. Clin Cancer Res 17:229–235. https://doi.org/10.1158/1078-0432.CCR-10-2276
Fargnoli MC, Gandini S, Peris K, Maisonneuve P, Raimondi S (2010) MC1R variants increase melanoma risk in families with CDKN2A mutations: a meta-analysis. Eur J Cancer 46:1413–1420. https://doi.org/10.1016/j.ejca.2010.01.027
Ford D et al (1995) Risk of cutaneous melanoma associated with a family history of the disease. The International Melanoma Analysis Group (IMAGE). Int J Cancer 62:377–381
Frants RR, van der Velden PA, Bergman W, Gruis NA (1996) Melanocyte-stimulating hormone receptor (MC1R) variants modify melanoma risk in Dutch FAMMM families. Am J Hum Genet Suppl 59:A67
Gandini S, Sera F, Cattaruzza MS, Pasquini P, Picconi O, Boyle P, Melchi CF (2005a) Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur J Cancer 41:45–60. https://doi.org/10.1016/j.ejca.2004.10.016
Gandini S et al (2005b) Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur J Cancer 41: 2040–2059. https://doi.org/10.1016/j.ejca.2005.03.034
Gibbs DC et al (2016) Association of Interferon Regulatory Factor-4 polymorphism rs12203592 with divergent melanoma pathways. J Natl Cancer Inst 108:djw004. https://doi.org/10.1093/jnci/djw004
Goldstein AM, Struewing JP, Chidambaram A, Fraser MC, Tucker MA (2000) Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations. J Natl Cancer Inst 92:1006–1010
Goldstein AM, Landi MT, Tsang S, Fraser MC, Munroe DJ, Tucker MA (2005) Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations. Cancer Epidemiol Biomark Prev 14:2208–2212. https://doi.org/10.1158/1055-9965.EPI-05-0321
Greene MH, Fraumeni JF (1979) The hereditary variant of malignant melanoma. In: Clark WH, Mastrangelo LJ, Goldman LI (eds) Human malignant melanoma. Grune & Stratton, New York, pp 139–166
Gu F et al (2018) Combining common genetic variants and non-genetic risk factors to predict risk of cutaneous melanoma. Hum Mol Genet. https://doi.org/10.1093/hmg/ddy282
Gudbjartsson DF et al (2008) ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma. Nat Genet 40:886–891. https://doi.org/10.1038/ng.161
Han J, Qureshi AA, Prescott J, Guo Q, Ye L, Hunter DJ, De Vivo I (2009) A prospective study of telomere length and the risk of skin cancer. J Invest Dermatol 129:415–421. https://doi.org/10.1038/jid.2008.238
Harland M et al (2014) Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom. Hered Cancer Clin Pract 12:20. https://doi.org/10.1186/1897-4287-12-20
Hasin Y, Seldin M, Lusis A (2017) Multi-omics approaches to disease. Genome Biol 18:83. https://doi.org/10.1186/s13059-017-1215-1
Hayward NK et al (2017) Whole-genome landscapes of major melanoma subtypes. Nature 545:175–180. https://doi.org/10.1038/nature22071
Hemminki K, Zhang H, Czene K (2003) Familial and attributable risks in cutaneous melanoma: effects of proband and age. J Invest Dermatol 120:217–223. https://doi.org/10.1046/j.1523-1747.2003.12041.x
Heppt MV et al (2017) Prognostic significance of BRAF and NRAS mutations in melanoma: a German study from routine care. BMC Cancer 17:536. https://doi.org/10.1186/s12885-017-3529-5
Hintzsche JD et al (2017) Whole-exome sequencing identifies recurrent SF3B1 R625 mutation and comutation of NF1 and KIT in mucosal melanoma. Melanoma Res 27:189–199. https://doi.org/10.1097/CMR.0000000000000345
Horn S et al (2013) TERT promoter mutations in familial and sporadic melanoma. Science 339:959–961. https://doi.org/10.1126/science.1230062
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. https://doi.org/10.1126/science.1229259
Iles MM et al (2013) A variant in FTO shows association with melanoma risk not due to. BMI Nat Genet 45(428–432):432e421. https://doi.org/10.1038/ng.2571
Iles MM et al (2014) The effect on melanoma risk of genes previously associated with telomere length. J Natl Cancer Inst 106. https://doi.org/10.1093/jnci/dju267
Johansson PA et al (2017) Mutation load in melanoma is affected by MC1R genotype. Pigment Cell Melanoma Res 30:255–258. https://doi.org/10.1111/pcmr.12571
Johnson DB, Puzanov I (2015) Treatment of NRAS-mutant melanoma. Curr Treat Options in Oncol 16:15. https://doi.org/10.1007/s11864-015-0330-z
Kamb A et al (1994) A cell cycle regulator potentially involved in genesis of many tumor types. Science 264:436–440
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 70:770–775. https://doi.org/10.1086/339076
Kanetsky PA et al (2006) Population-based study of natural variation in the melanocortin-1 receptor gene and melanoma. Cancer Res 66:9330–9337
Kanetsky PA, Panossian S, Elder DE, Guerry D, Ming ME, Schuchter L, Rebbeck TR (2010) Does MC1R genotype convey information about melanoma risk beyond risk phenotypes? Cancer 116:2416–2428. https://doi.org/10.1002/cncr.24994
Keller MC (2014) Gene x environment interaction studies have not properly controlled for potential confounders: the problem and the (simple) solution. Biol Psychiatry 75:18–24. https://doi.org/10.1016/j.biopsych.2013.09.006
Kiuru M, Busam KJ (2017) The NF1 gene in tumor syndromes and melanoma. Lab Investig 97:146–157. https://doi.org/10.1038/labinvest.2016.142
Kosiniak-Kamysz A, Marczakiewicz-Lustig A, Marcinska M, Skowron M, Wojas-Pelc A, Pospiech E, Branicki W (2014) Increased risk of developing cutaneous malignant melanoma is associated with variation in pigmentation genes and VDR, and may involve epistatic effects. Melanoma Res 24:388–396. https://doi.org/10.1097/CMR.0000000000000095
Kruglyak L (1999) Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat Genet 22:139–144. https://doi.org/10.1038/9642
Landreville S et al (2012) Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. Clin Cancer Res 18:408–416. https://doi.org/10.1158/1078-0432.CCR-11-0946
Law MH et al (2015) Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma. Nat Genet 47:987–995. https://doi.org/10.1038/ng.3373
Li C et al (2006) Genetic variants of the ADPRT, XRCC1 and APE1 genes and risk of cutaneous melanoma. Carcinogenesis 27:1894–1901. https://doi.org/10.1093/carcin/bgl042
Li X et al (2013) Obesity-related genetic variants, human pigmentation, and risk of melanoma. Hum Genet 132:793–801. https://doi.org/10.1007/s00439-013-1293-4
Li X, Liu H, Amos CI, Lee JE, Thomas NE, Wei Q, Han J (2017) A PGC1beta genetic variant associated with nevus count and melanoma mortality. Int J Cancer 141:1066–1067. https://doi.org/10.1002/ijc.30802
Macgregor S et al (2011) Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3. Nat Genet 43:1114–1118. https://doi.org/10.1038/ng.958
Maertens O et al (2013) Elucidating distinct roles for NF1 in melanomagenesis. Cancer Discov 3:338–349. https://doi.org/10.1158/2159-8290.CD-12-0313
Martin AR et al (2017) An unexpectedly complex architecture for skin pigmentation in Africans. Cell 171:1340–1353 e1314. https://doi.org/10.1016/j.cell.2017.11.015
Mauguen A, Zabor EC, Thomas NE, Berwick M, Seshan VE, Begg CB (2017) Defining Cancer Subtypes With Distinctive Etiologic Profiles: An Application to the Epidemiology of Melanoma. J Am Stat Assoc 112(517):54–63
Mucci LA et al (2016) Familial risk and heritability of Cancer among twins in Nordic countries. JAMA 315:68–76. https://doi.org/10.1001/jama.2015.17703
Nan H et al (2011) Shorter telomeres associate with a reduced risk of melanoma development. Cancer Res 71:6758–6763. https://doi.org/10.1158/0008-5472.CAN-11-1988
Newton-Bishop JA et al (2010) Melanocytic nevi, nevus genes, and melanoma risk in a large case-control study in the United Kingdom. Cancer Epidemiol Biomark Prev 19:2043–2054. https://doi.org/10.1158/1055-9965.EPI-10-0233
Norris W (1820) A Case of fungoid disease. Edinb Med Sur J 16:562–565
Olsen CM, Carroll HJ, Whiteman DC (2010a) Estimating the attributable fraction for cancer: a meta-analysis of nevi and melanoma. Cancer Prev Res (Phila) 3:233–245. https://doi.org/10.1158/1940-6207.CAPR-09-0108
Olsen CM, Carroll HJ, Whiteman DC (2010b) Estimating the attributable fraction for melanoma: a meta-analysis of pigmentary characteristics and freckling. Int J Cancer 127:2430–2445. https://doi.org/10.1002/ijc.25243
Olsen CM, Carroll HJ, Whiteman DC (2010c) Familial melanoma: a meta-analysis and estimates of attributable fraction. Cancer Epidemiol Biomark Prev 19:65–73. https://doi.org/10.1158/1055-9965.EPI-09-0928
Olsen CM et al (2018) Risk stratification for melanoma: models derived and validated in a purpose-designed prospective cohort. J Natl Cancer Inst 110:1075. https://doi.org/10.1093/jnci/djy023
Onken MD, Worley LA, Long MD, Duan S, Council ML, Bowcock AM, Harbour JW (2008) Oncogenic mutations in GNAQ occur early in uveal melanoma. Invest Ophthalmol Vis Sci 49:5230–5234. https://doi.org/10.1167/iovs.08-2145
Palmer JS et al (2000) Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype? Am J Hum Genet 66:176–186. https://doi.org/10.1086/302711
Park JJ, Diefenbach RJ, Joshua AM, Kefford RF, Carlino MS, Rizos H (2018) Oncogenic signaling in uveal melanoma. Pigment Cell Melanoma Res 31:661. https://doi.org/10.1111/pcmr.12708
Pasquali E et al (2015) MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project. Int J Cancer 136:618–631. https://doi.org/10.1002/ijc.29018
Pomerantz J et al (1998) The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2′s inhibition of p53. Cell 92:713–723
Rafnar T et al (2009) Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41:221–227. https://doi.org/10.1038/ng.296
Raimondi S, Sera F, Gandini S, Iodice S, Caini S, Maisonneuve P, Fargnoli MC (2008) MC1R variants, melanoma and red hair color phenotype: a meta-analysis. Int J Cancer 122:2753–2760. https://doi.org/10.1002/ijc.23396
Read J, Wadt KA, Hayward NK (2016) Melanoma genetics. J Med Genet 53:1–14. https://doi.org/10.1136/jmedgenet-2015-103150
Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273: 1516–1517
Rivas MA et al (2011) Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet 43: 1066–1073. https://doi.org/10.1038/ng.952
Robertson AG et al (2017) Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell 32:204–220 e215. https://doi.org/10.1016/j.ccell.2017.07.003
Robles-Espinoza CD et al (2014) POT1 loss-of-function variants predispose to familial melanoma. Nat Genet 46:478–481. https://doi.org/10.1038/ng.2947
Robles-Espinoza CD et al (2016) Germline MC1R status influences somatic mutation burden in melanoma. Nat Commun 7:12064. https://doi.org/10.1038/ncomms12064
Sakaizawa K et al (2015) Clinical characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients. J Dermatol Sci 80:33–37. https://doi.org/10.1016/j.jdermsci.2015.07.012
Scheuermann JC et al (2010) Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465:243–247. https://doi.org/10.1038/nature08966
Shain AH et al (2015) Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway. Nat Genet 47:1194–1199. https://doi.org/10.1038/ng.3382
Shen J, Song R, Wan J, Huff C, Fang S, Lee JE, Zhao H (2017) Global methylation of blood leukocyte DNA and risk of melanoma. Int J Cancer 140:1503–1509. https://doi.org/10.1002/ijc.30577
Shi J et al (2014) Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma. Nat Genet 46:482–486. https://doi.org/10.1038/ng.2941
Smit AK et al (2017) A pilot randomized controlled trial of the feasibility, acceptability, and impact of giving information on personalized genomic risk of melanoma to the public. Cancer Epidemiol Biomark Prev 26:212–221. https://doi.org/10.1158/1055-9965.EPI-16-0395
Smit AK et al (2018) The melanoma genomics managing your risk study: a protocol for a randomized controlled trial evaluating the impact of personal genomic risk information on skin cancer prevention behaviors. Contemp Clin Trials 70:106–116. https://doi.org/10.1016/j.cct.2018.05.014
Stratton MR, Campbell PJ, Futreal PA (2009) The cancer genome. Nature 458:719–724. https://doi.org/10.1038/nature07943
Sulem P et al (2008) Two newly identified genetic determinants of pigmentation in Europeans. Nat Genet 40:835–837. https://doi.org/10.1038/ng.160
Thomas NE et al (2015) Association between NRAS and BRAF mutational status and melanoma-specific survival among patients with higher-risk primary melanoma. JAMA Oncol 1:359–368. https://doi.org/10.1001/jamaoncol.2015.0493
Thomas NE et al (2017) Associations of MC1R genotype and patient phenotypes with BRAF and NRAS mutations in melanoma. J Invest Dermatol 137:2588–2598. https://doi.org/10.1016/j.jid.2017.07.832
Thomas NE et al (2018) Inherited genetic variants associated with melanoma BRAF/NRAS subtypes. J Invest Dermatol 138:2398. https://doi.org/10.1016/j.jid.2018.04.025
Tsao H, Sober AJ, Barnhill RL (1997) Desmoplastic neurotropic melanoma. Semin Cutan Med Surg 16: 131–136
Tsao H, Goel V, Wu H, Yang G, Haluska FG (2004) Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma. J Invest Dermatol 122:337–341
Valverde P et al (1996) The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma. Hum Mol Genet 5:1663–1666
Van Raamsdonk CD et al (2009) Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457:599–602. https://doi.org/10.1038/nature07586
Van Raamsdonk CD et al (2010) Mutations in GNA11 in uveal melanoma. N Engl J Med 363:2191–2199. https://doi.org/10.1056/NEJMoa1000584
Vanderweele TJ, Mukherjee B, Chen J (2012) Sensitivity analysis for interactions under unmeasured confounding. Stat Med 31:2552–2564. https://doi.org/10.1002/sim.4354
Vuong K, McGeechan K, Armstrong BK, Cust AE (2014) Risk prediction models for incident primary cutaneous melanoma: a systematic review. JAMA Dermatol 150:434–444. https://doi.org/10.1001/jamadermatol.2013.8890
Vuong K et al (2016) Development and external validation of a melanoma risk prediction model based on self-assessed risk factors. JAMA Dermatol 152:889–896. https://doi.org/10.1001/jamadermatol.2016.0939
Vuong K, Armstrong BK, McGeechan K, Cust AE (2018) Personalized melanoma risk assessments and tailored prevention advice: a pragmatic randomized controlled trial in Australian general practice. Fam Pract. https://doi.org/10.1093/fampra/cmy040
Wachsmuth RC, Harland M, Bishop JA (1998) The atypical-mole syndrome and predisposition to melanoma. N Engl J Med 339:348–349. https://doi.org/10.1056/NEJM199807303390515
Wachsmuth RC et al (2001) Heritability and gene-environment interactions for melanocytic nevus density examined in a U.K. adolescent twin study. J Invest Dermatol 117:348–352. https://doi.org/10.1046/j.0022-202x.2001.01415.x
Watts CG et al (2017) Clinical features associated with individuals at higher risk of melanoma: a population-based study. JAMA Dermatol 153:23–29. https://doi.org/10.1001/jamadermatol.2016.3327
Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678. https://doi.org/10.1038/nature05911
Whittaker SR et al (2013) A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition. Cancer Discov 3:350–362. https://doi.org/10.1158/2159-8290.CD-12-0470
Wiesner T et al (2011) Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet 43: 1018–1021. https://doi.org/10.1038/ng.910
Wiesner T et al (2012) Toward an improved definition of the tumor spectrum associated with BAP1 germline mutations. J Clin Oncol 30:e337–e340. https://doi.org/10.1200/JCO.2011.41.2965
Wilmott JS et al (2018) Whole genome sequencing of melanomas in adolescent and young adults reveals distinct mutation landscapes and the potential role of germline variants in disease susceptibility. Int J Cancer. https://doi.org/10.1002/ijc.31791
Wu YP et al (2018) Melanoma risk assessment based on relatives’ age at diagnosis. Cancer Causes Control 29:193–199. https://doi.org/10.1007/s10552-017-0994-8
Xiao F, Ma J, Cai G, Fang S, Lee JE, Wei Q, Amos CI (2014) Natural and orthogonal model for estimating gene-gene interactions applied to cutaneous melanoma. Hum Genet 133:559–574. https://doi.org/10.1007/s00439-013-1392-2
Yokoyama S et al (2011) A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature 480:99–103. https://doi.org/10.1038/nature10630
Yu Y et al (2018) Integrated case-control and somatic-germline interaction analyses of melanoma susceptibility genes. Biochim Biophys Acta 1864:2247–2254. https://doi.org/10.1016/j.bbadis.2018.01.007
Zhu G et al (1999) A major quantitative-trait locus for mole density is linked to the familial melanoma gene CDKN2A: a maximum-likelihood combined linkage and association analysis in twins and their sibs. Am J Hum Genet 65:483–492. https://doi.org/10.1086/302494
Zuo L et al (1996) Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet 12:97–99. https://doi.org/10.1038/ng0196-97
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Cust, A.E., Tsao, H., Berwick, M., Mann, G.J., Iles, M.M. (2020). Molecular Epidemiology of Melanoma. In: Balch, C., et al. Cutaneous Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-030-05070-2_48
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DOI: https://doi.org/10.1007/978-3-030-05070-2_48
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