Genes involved in melanoma: An overview of INK4a and other loci

Melanoma Research

Volumn 9, Issue 5, 1999, Pages 421-432

  Castellano, M ^a   Parmiani, G ^a  

^a NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

Deletion; Familial melanoma; Gene; Locus; Mutation; Sporadic melanoma

Indexed keywords

BETA CATENIN; MELANOCORTIN RECEPTOR; MYC PROTEIN; PROTEIN P16; RAS PROTEIN; RECEPTOR SUBTYPE;

CANCER GROWTH; CHROMOSOME 10Q; CHROMOSOME 11Q; CHROMOSOME 1P; CHROMOSOME 6; CHROMOSOME 9P; FAMILIAL CANCER; GENE FUNCTION; GENE LOCATION; GENE LOCUS; GENETIC SUSCEPTIBILITY; HUMAN; MELANOMA; PRIORITY JOURNAL; REVIEW; SKIN CARCINOGENESIS; TUMOR SUPPRESSOR GENE; ULTRAVIOLET IRRADIATION;

EID: 0032717587     PISSN: 09608931     EISSN: None     Source Type: Journal    
DOI: 10.1097/00008390-199910000-00001     Document Type: Review

References (112)

1. Cannon-Albright LA, Goldgar DE, Meyer LJ, Lewis CM, Anderson DE, Fountain JW, Hegi ML, Wiseman RW, Petty EM, Bale AE, Olopade OI, Diaz MO, Kwiatkowski DJ, Piepkorn MW, Zone JJ, Skolnick MH. Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22. Science 1992; 258: 1148-1152.
2. Bale SJ, Dracopoli NC, Tucker MA, Clark WH Jr, Fraser MC, Stanger BZ, Green P, Donis-Keller H, Housman DE, Greene MH. Mapping the gene for hereditary cutaneous malignant melanoma-dysplastic nevus syndrome to chromosome 1p. New Engl J Med 1989; 320:1367-1372.
3. Nancarrow DJ, Walker GJ, Weber JL, Walters MK, Palmer JM, Hayward NK. Linkage mapping of melanonia (MLM) using 172 microsatellite markers. Genomics 1992; 14: 939-947.
4. Walker GJ, Nancarrow DJ, Walters MK, Palmer JM, Weber JL, Hayward NK. Linkage analysis in familial melanoma kindreds to markers on chromosome 6p. Int J Cancer 1994; 59: 771-775.
5. Albino AP. Genes involved in melanoma susceptibility and progression. Curr Opin Oncol 1995; 7: 162-169.
6. Herbst RA, Weiss J, Ehnis A, Cavenee WK, Arden KC. Loss of heterozygosity for 10q22-10qter in malignant melanoma progression. Cancer Res 1994; 54: 3111-3114.
7. Robertson G, Coleman A, Lugo TG. A malignant melanoma tumor suppressor on human chromosome 11. Cancer Res 1996; 56: 4487-4492.
8. Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS III, Johnson BE, Skolnick MH. A cell cycle regulator potentially involved in genesis of many tumor types. Science 1994; 264: 436-440.
9. Nobori T, Miura K, Wu DJ, Lois A, Takabuyashi K, Carson DA. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 1994; 368: 753-756.
10. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV. Identification of a candidate tumor suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nature Genet 1997; 15: 356-362.
11. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombic R, Bigner SH, Giovanella BC, Ittmann M, Tycko R, Hibshoosh H, Wigler MH, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997; 275: 1943-1947.
12. Meier F, Satyamoorthy K, Nesbit M, Hsu M-Y, Schittek B, Garbe C, Herlyn M. Molecular events in melanoma development and progression. Front Biosci 1998; 3: 1005-1010.
13. Hayward NK. The current situation with regard to human melanoma and genetic inferences. Curr Opin Biol 1996; 8: 136-142.
14. Serrano M. The tumor suppressor protein n16INK4a. Exp Cell Res 1997; 237: 7-13.
15. Mao L, Merlo A, Bedi G, Shapiro GI, Edwards CD, Rollins BJ, Sidransky D. A novel p16 INK4a transcript. Cancer Res 1995; 55: 2995-2997.
16. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclinD/CDK4. Nature 1993; 366: 704-707.
17. Lukas J, Parry D, Aagaard L, Mann DJ, Bartkova J, Strauss M, Peters C, Bartek J. Retinoblastoma-protein-dependent cell-cycle inhibition by the tumor suppressor p16. Nature 1995; 375: 503-510.
18. Koh J, Enders GH, Dynlacht BD, Harlow E. Tumor-derived p16 alleles encoding proteins defective in cell-cycle inhibition. Nature 1995; 375: 506-510.
19. Ranade K, Hussussian CJ, Sikorski RS, Varmus HE, Goldstein AM, Tucker MA, Serrano M, Hannon GJ, Beach D, Dracopoli NC. Mutations associated with familial melanoma Impair p16INK4 function. Nature Genet 1995; 10: 114-116.
20. Parry D, Peters G, Temperature-sensitive mutants of p16CDKN2 associated with familial melanoma. Mol Cell Biol 1996; 16: 3844-3852.
21. Harland M, Meloni R, Gruis N, Pinney E, Brookes S, Spurr NK, Frischauf A-M, Bataille V, Peters G, Cuzick J, Selby P, Bishop DT, Bishop JN, Germline mutations of the CDKN2 gene in UK melanoma families. Hum Mol Genet 1997; 6: 2061-2067.
22. Reymond A, Brent R. p16 proteins from melanoma-prone families are deficlent in binding to Cdk4. Oncogene 1995; 11: 1173-1178.
23. Walker GJ, Gabrielli BG, Castellano M, Hayward NK. Functional reassessment of p16 variants using a transfection-based assay. Int J Cancer 1999 (in press).
24. MacKie RM, Andrew N, Lanyon WG, Connor JM. CDKN2A germline mutations in UK patients with familial melanoma and multiple primary melanoma. J Invest Dermatol 1998; 111: 269-272.
25. Monzon J, Liu L, Brill H, Goldstein AM, Tucker MA, From L, McLaughlin J, Hogg D, Lassam NJ. CDKW2A mutations in multiple primary melanomas. New Engl J Med 1998; 338: 879-887.
26. Foulkes WD, Flanders TY, Pollock PM, Hayward NK. The CDKN2A/P16 gene and human cancer. Mol Med 1997; 3: 5-20.
27. Liu L, Dilworth D, Gao L, Monzon J, Summers A, Lassam N, Hogg D. Mutation of the CDKN2A 5' UTR creates an aberrant initiation codon and predisposes to melanoma. Nature Genet 1999; 21: 128-132.
28. FitzGerald MG, Harkin DP, Silva-Arrieta S, MacDonald DJ, Lucchina LC, Unsal H, O'Neill E, Koh J, Finkelstein DM, Isselbacher KJ, Sober AJ, Haber DA. Prevalence of germ-line mutations in p16 p19ARF, and CDK4 in familial melanoma: analysis of a clic-based population. Proc Natl Acad Sci USA 1996; 93: 8541-8545.
29. Flores JF, Pollock PM, Walker GJ, Glendening JM, Lin AH, Palmer JM, Walters MK, Hayward NK, Fountain JW. Analysis of the CDKN2A, CDKN2B and CDK4 genes in 48 Australian melanoma kindreds. Oncogene 1997; 15:2999-3005.
30. Platz A, Hansson J, Mansson-Brahme E, Lagerlof B, Linder S, Lundqvist E, Sevigny P, Inganas M, Ringborg U. Screening of germline mutations in the CDKN2A and CDKN2B genes in Swedish families with hereditary cutancous melanoma. J Natl Cancer Inst 1997; 89: 697-702.
31. Fargnoli MC, Chimenti S, Keller G, Soyer HP, Dal Pozzo V, Hofler H, Pern, K. CDKN2a/p16INK4a mutations and lack of p19ARF involvement in familial melanoma kindreds. J Invest Dermatol 1998; 111:1202-1206.
32. Aitken J, Welch J, Duffy D, Milligan A, Green A, Martin N, Hayward N. CDKN2A variants in a population-based sample of Queensland families with melanoma. J Natl Cancer Inst 1999; 91: 446-452.
33. Castellano M, Pollock PM, Walters MK, Sparrow LE, Down LM, Gabrielli BG, Parsons PG, Hayward NK. CDKN2A/p16 is inactivated in most melanoma cell lines. Cancer Res 1997; 57: 4868-4875.
34. Healy E, Sikkink S, Rees JL. Infrequent mutation of p16INK4 in sporadic melanoma. J Invest Dermatol 1996; 107: 318-321.
35. Wagner SN, Wagner C, Briedigkeit L, Goos M. Homozygous deletion of the p16INK4a and the p15INK4b tumour suppressor genes in a subset of human sporadic cutaneous malignant melanomas. Br J Dermatol 1998; 138: 13-21.
36. Pollock PM, et al. Evidence of UV induction of CDKN2 mutations in melanoma cell lines. Oncogene 1995; 11: 663-668.
37. Keller-Melchior R, Schmidt R, Piepkorn M. Expression of the tumor suppressor gene product p16INK4 In benign and malignant melanocyte lesions. J Invest Dermatol 1998; 110: 932-938.
38. Castellano M, Gabrielli BG, Hussussian CJ, Dracopoli NC, Hayward NK. Restoration of CDKN2A into melanoma cells induces morphologic changes and reduction in growth rate but not anchorage-independent growth reversal. J Invest Dermatol 1997; 109: 61-68.
39. Serrano M, Lee H, Chin L, Cordon-Cardo C, Beach D, DePinho RA. Rolf for the INK4 locus in rumor suppression and cell mortality. Cell 1996; 85: 27-37.
40. Chin L, Pomerantz J, Polsky D, Jacobson M, Cohen C, Cordon-Cardo C, Horner JW II, DePinho RA. Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Genes Dev 1997; 11: 2822-2834.
41. Hara E, Smith R, Parry D, Tahara H, Stone S, Peters G. Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence. Mol Cell Biol 1996; 16: 859-867.
42. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997; 88: 593-602.
43. Noble JR, Rogan EM, Neumann AA, Maclean K, Bryan TM, Reddel RR. Association of extended in vitro proliferative potential with loss of p16INK4 expression. Oncogene 1996; 13: 1259-1268.
44. Stone S, Jiang P, Dayananth P, Tavtigian SV, Katcher H, Parry D, Peters G, Kamb A. Complex structure and regulation of the p16 (MTS1) locus. Cancer Res 1995; 55: 2988-2994.
45. Quelle DE, Zindy F, Ashmun RA, Sherr CJ. Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell 1995; 83: 993-1000.
46. Zhang Y, Xiong Y, Yarbrough WG. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 1998; 92: 725-734.
47. Pomerantz J, Schreiber-Agus N, Liegeois NJ, Silverman A, Alland L, Chin L, Potes J, Chen K, Orlow I, Lee HW, Cordon-Cardo C, DePinho RA. The Ink4a tumor suppressor gene product, p19ARF, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell 1998; 92: 713-723.
48. Stott FJ, Bates S, James MC, McConnell BB, Starborg M, Brookes S, Palmero I, Ryan K, Hara E, Vousden KH, Peters G. The alternative product from the human CDKN2A locus, p14ARF, participates in a regulatory feedback loop with p53 and MDM2. EMBO J 1998; 17: 5001-5014.
49. Kamijo T, Weber JD, Zambetti G, Zindy F, Roussel MF, Sherr CJ. Functional and physical interactions of the ARF tumor suppressor with p53 and MDM2. Proc Natl Acad Sci USA 1998; 95: 8292-8297.
50. Palmero I, Pantoja C, Serrano M. p19ARF links the tumour suppressor p53 to Ras. Nature 1998; 395: 125-126.
51. Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL, Vousden KH. p14ARF links the tumour suppressors RB and p53. Nature 1998; 395: 124-125.
52. Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR, Ashmun RA, Grosveld G, Sherr CJ. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 1997; 91: 649-659.
53. Quelle DE, Cheng M, Ashmun RA, Sherr CJ. Cancer associated mutations at the INK4a locus cancel cell cycle arrest by p16INK4a but not by the alternative reading frame protein p19ARF. Proc Natl Acad Sci USA 1997; 94: 669-673.
54. Kumar R, Sauroja I, Punnonen K, Jansen C, Hemmiki K. Selective deletion of exon 1β of the p19ARF gene in metastatic melanoma cell lines. Genes Chromosome Cancer 1998; 23: 273-277.
55. Stone S, Dayananth P, Jiang P, Weaver-Feldhaus JM, Tavtiglan SV, Cannon-Albright L, Kamb A. Genomic structure, expression and mutational analysis of the p15 (MTS2) gene. Oncogene 1995; 11: 987-991.
56. Hannon GJ, Beach D. p15INK4B is a potential effector of TGF-B-induced cell cycle arrest. Nature 1994; 371: 257-261.
57. Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H. Mutations of p16 and p15 tumor suppressor genes and replication errors contribute independently to the pathogenesis of sporadic malignant melanoma. Arch Dermatol Res 1998; 290: 175-180.
58. Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Buschenfelde KH, Beach D. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 1995; 269: 1281-1284.
59. Tsao H, Benoit E, Sober AJ, Thiele C, Haluska FG. Novel mutations in the p16/CDKN2A binding region of the cyclin-dependent kinase-4 gene. Cancer Res 1998; 58: 109-113.
60. Soufir N, Avril M-F, Chompret A, Demenais F, Bombled J, Spatz A, Stoppa-Lyonnet D, French Familial Melanoma Study Group, Benard J, Bressac-de Paillerets B. Prevalence of p16 und CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group. Hum Mol Genet 1998; 7: 209-216.
61. Traboulsi EI, Zimmerman LE, Manz HJ. Cutaneous malignant melanoma in survivors of heritable retino-blastoma. Arch Ophthalmol 1988; 106: 1059-1061.
62. Bartkova J, et al. The p16-cyclin D/Cdk4-Rb pathway as a functional unit frequently altered in melanoma pathogenesis. Cancer Res 1996; 56: 5475-5483.
63. Akslen LA, Monstad SE, Larsen B, Straume O, Ogreid D. Frequent mutations of the p53 gene in cutaneous melanoma of the nodular type. Int J Cancer (Pred Oncol) 1998; 79: 91-95.
64. Whiteman DC, Parsons PG, Green AC. p53 expression and risk factors for cutaneous melanoma: a case control study. Int J Cancer 1998; 77: 843-848.
65. Cannon-Albright LA, Goldgar DE, Wright EC, Turco A, Jost M, Meyer LJ, Piepkorn M, Zone JJ, Skolnick MH. Evidence against the reported linkage of the cutaneous melanoma-dysplastic nevus syndrome locus to chromosome 1p36. Am J Hum Genet 1990; 46: 912-918.
66. Nancarrow DJ, Palmer JM, Walters MK, Kerr BM, Hafner GJ, Garske L, McLeod GR, Hayward NK. Exclusion of the familial melanoma locus (MLM) from the PND/D1S47 and MYCL1 regions of chromosome arm 1p in 7 Australian pedigrees. Genomics 1992; 12: 18-25.
67. Goldstein AM, Goldin LR, Dracopoli NC, Clark WH Jr, Tucker MA. Two-locus linkage analysis of cutaneous malignant melanoma/dysplastic nevi. Am J Hum Genet 1996; 58: 1050-1056.
68. Holland EA, Beaton SC, Kefford RF, Mann GJ. Linkage analysis of familial melanoma and chromosome 6 in 14 Australian kindreds. Genes Chromosome Cancer 1997; 19: 241-249.
69. Vidal MJ, Loganzo F Jr, de Oliveira AR, Hayward NK, Albino AP. Mutations and defective expression of the WAF1 p21 tumour-suppressor gene in malignant melanomas. Melanoma Res 1995; 5: 243-250.
70. Zhang J, Cui P, Glatfelter AA, Cummings LM, Meltzer PS, Trent JM. Microdissection based cloning of a translocation breakpoint in human malignant melanoma. Cancer Res 1995; 55: 4640-4645.
71. Walker GJ, Palmer JM, Walters MK, Nancarrow DJ, Parsons PG, Hayward NK. Simple tandem repeat allelic deletions confirm the preferential loss of distal chromosome 6q in melanoma. Int J Cancer 1994b; 58: 203-206.
72. Trent JM, Stanbridge EJ, McBride HL, Meese EU, Casey G, Araujo DE, Witkowski CM, Nagle RB. Tumorigenicity in human melanoma cell lines controlled by introduction of human chromosome 6. Science 1990; 247: 568-571.
73. Myers MP, Stolarov JP, Eng C. Li J, Wang SI, Wigler MH, Parsons R, Tonks NK. P-TEN, the rumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc Natl Acad Sci USA1997; 94: 9052-9057.
74. Li D-M, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor B. Cancer Res 1997; 57: 2124-2129.
75. Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP. Pten is essential for embryonic development and tumour suppression. Nature Genet 1998; 19: 348-355.
76. Guldberg P, thor Straten P, Birck A, Ahrenkiel V, Kirkin AF, Zeuthen J. Disruption of the MMAC1/PTEN gene by deletion or mutartion is a frequent event in malignant melanoma. Cancer Res 1997; 57: 3660-3663.
77. Teng DH, Hu R, Lin H, Davis T, Iliev D, Frye C, Swedlund B, Hansen KL, Vinson VL, Gumpper KL, Ellis L, El-Naggar A, Frazler M, Jasser S, Langford LA, Lee J, Mills GB, Pershouse MA, Pollack RE, Tornos C, Troncoso P, Yung WK, Fujii G, Berson A, Steck PA, et al. MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer Res 1997; 57: 5221-5225.
78. Robertson GP, Furnari FB, Miele ME, Glendening MJ, Welch DR, Fountain JW, Lugo TG, Huang HJ, Cavenee WK. In vitro loss of heterozygosity targets the PTEN/MMAC1 gene in melanoma. Proc Natl Acad Sci USA 1998; 95: 9418-9423.
79. Tomlison IPM, et al. Allele loss on chromosome IIq and microsatellite instability in malignant melanoma. Eur J Cancer 1996; 32A: 1797-1802.
80. Herbst RA, Larson A, Weiss J, Cavenee WK, Hampton GM, Arden KC. A defined region of loss of heterozygosity at IIq23 in cutanrous malignant melanoma. Cancer Res 1995; 55: 2494-2496.
81. Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J, Evans GA. Alterations of the PPP2R1B gene in human lung and colon cancer. Science 1998; 282: 284-287.
82. Van't Veer IJ, Burgering BMT, Versteeg R, Boot AJM, Ruiter DJ, Osanto S, Schrier PI, Bos JL. N-ras mutations in human cutaneous melanoma from sun-exposed body sites. Mol Cell Biol 1989; 9: 3114-3116.
83. Wagner SN, Ockenfels HM, Wagner C, Hofler H, Goos M. Ras gene mutations: a rare event in nonmetastatic primary malignant melanoma. J Invest Dermatol 1995; 104: 868-871.
84. Jafari M, Papp T, Kirchner S, Diener U, Henschler D, Burg G, Schiffmann D. Analysis of ras mutations in human melanocytic lesions: activation of the ras gene seems to be associated with the nodular type of human malignant melanoma. J Cancer Res Clin Oncol 1995; 121: 23-30.
85. Jiveskog S, Ragnarsson-Olding B, Platz A, Ringborg U. N-ras mutations are common in melanomas from sunexposed skin of humans but rare in mucosal membranes or unexposed skin. J Invest Dermatol 1998; 111: 757-761.
86. Albino AP, Sozzi G, Nanus DM, Jhanwar SC, Houghton AN. Malignant transformation of human melanocytes: induction of a complete melanoma phenotype and genotype. Oncogene 1992; 7: 2315-2321.
87. Powell MB, Hyman P, Bell OD, Balmain A, Brown K, Alberts D, Bowden GT. Hyperpigmentation and melanocytic hyperplasia in transgenic mice expressing the human T24 Ha-ras gene regulated by a mouse tyrosinase promoter. Mol Carcinog 1995; 12: 82-90.
88. Gause PR, Lluria-Prevatt M, Keith WN, Balmain A, Linardopolous S, Warneke J, Powell MB. Chromosomal and genetic alterations of 7,12-dimethylbenz(a)anthracene-induccd melanoma from TP-ras transgenic mice. Mol Carcinog 1977; 20: 78-87.
89. Ross DA, Wilson GD. Expression of c-myc oncoprotein represents a new prognostic marker in cutaneous melanoma. Br J Surg 1998; 85: 46-51.
90. Schlagbauer-Wadl H, Griffioen M, van Elsas A, Schrier PI, Pustelnik T, Eichler HG, Wolff K, Pehamberger H, Jansen B. Influence of increased c-Myc expression on the growth characteristics of human melanoma. J Invest Dermatol 1999; 112: 332-336.
91. Konstadoulakis MM, Vezeridis M, Hatziyianni E, Karakousis CP, Cole B, Bland KI, Wanebo HJ. Molecular oncogene markers and their significance in cutaneous malignant melanoma. Ann Surg Oncol 1998; 5: 253-260.
92. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW. Identification of c-myc as a target of the APC pathway. Science 1998; 281: 1509-1512.
93. Robbins PF, El-Gamil M, Li YF, Kawakami Y, Loftus D, Appella E, Rosenberg SA. A mutated B-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med 1996; 183: 1185-1192.
94. Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri F, Polakis P. Stabilization of B-catenin by genetic defects in melanoma cell lines. Science 1997; 275: 1790-1792.
95. 4DPheaMSH increases the eumelanin-phaeomelanin ratio in cultured human melanocytes. J Invest Dermatol 1995; 104: 83-55.
96. Valverde P, Healy E, Jackson I, Rees JL, Thody AJ. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nature Genet 1995; 11: 328-330.
97. Valverde P, Healy E, Sikkink S, Haldane F, Thody AJ, Carothers A, Jackson IJ, Rees JL. The Asp48Glu variant of the melanocortin receptor (MC1R) is associated with melanoma. Hum Mol Genet 1996; 5: 1663-1666.
98. Healy E, Todd C, Jackson IJ, Birch-Machin M, Rees JL. Skin type, melanoma and melanocortin 1 receptor variants. J Invest Dermatol 1999; 112: 512-513.
99. Walker GJ, Hussussian CJ, Flores JF, Glendening JM, Haluska FG, Dracopoli NC, Hayward NK, Fountain JW. Mutations of the CDKN2A/p16INK4 gene in Australian melanoma kindreds. Hum Mol Genet 1995; 4: 1845-1852
100. Holland EA, Beaton SC, Becker TM, Grulet OMC, Peters BA, Rizos H, Kefford RF, Mann GJ. Analysis of the p16 gene, CDKN2, in 17 Australian melanoma kindreds. Oncogene 1995; 11: 2289-2294.
101. Hussussian CJ, Struewing JP, Goldstein AM, Higgins PAT, Ally DS, Sheahan MD, Clark WH Jr, Tucker MA, Dracopoli NC. Germline p16 mutations in familial melanoma. Nature Genet 1994; 8: 15-21.
102. Liu L, Lassam NJ, Slingerland JM, Bailey D, Cole D, Jenkins R, Hogg R. Germline p16INK4A mutation and protein dysfunction in a family with inherited melanoma. Oncogene 1995; 11: 405-412.
103. Whelan AJ, Bartsch D, Goodfellow PJ. A familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene. New Engl J Med 1995; 333: 975-977.
104. Ciotti P, Strigini P, Bianchi-Scarra G. Familial melanoma and pancreatic cancer. N Engl J Med 1996; 334: 469-470.
105. Puig S, Ruiz A, Castel T, Volpini V, Malvehy J, Cardellach F, Lynch M, Mascaro JM, Estivill X. Inherited susceptibility to several cancers but absence of linkage between dysplastic nevus syndrome and CDKN2A in a melanoma family with a mutation in the CDKN2A (p16INK4A) gene. Hum Genet 1997; 101: 359-364.
106. Gruis N, van der Velden PA, Sandkuijl LA, Prins DE, Weaver-Feldhaus J, Kamb A, Bergman W, Frants RR. Homozygotes for CDKN2(p16) germline mutation in Dutch familial melanoma kindreds. Nat Genet 1995; 10: 351-353.
107. Goldstein AM, Fraser MC, Struewing JP, Hussussian CJ, Ranade K, Zametkin DP, Fontaine LS, Organic SM, Dracopoli NC, Clark WH Jr, Tucker MA. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N Engl J Med 1995; 333: 970-974.
108. Whiteman DC, Milligan A, Welch J, Green AC, Hayward NK. Germline CDKN2A mutations in childhood melanoma. J Natl Inst Cancer 1997; 89: 1460.
109. Sun S, Pollock PM, Liu L, Karimi S, Jothy S, Milner BJ, Renwick A, Lassam NJ, Hayward NK, Hogg D, Narod SA, Foulkes WD. CDKN2A mutation in a non-FAMMM kindred with cancers at multiple sites results in a functionally abnormal protein. Int J Cancer 1997; 73: 531-536.
110. Yarbrough WG, Aprelikova O, Pei H, Olshan AF, Liu ET. Familial tumor syndrome associated with a germline nonfunctional p16INK4a allele. J Natl Cancer Inst 1996; 88: 1489-1491.
111. Yakobson EA, Zlotogorski A, Shafir R, Cohen M, Icekson M, Landau M, Brenner S, Usher S, Peretz H. Screening for tumour suppressor p16(CDKN2A) germline mutations in Israeli melanoma families. Clin Chem Lab Med 1998; 36: 645-648.
112. Borg A, Johansson U, Johansson O, Hakansson S, Westerdhal J, Masback A, Olsson H, Ingvar C. Novel germline p16 mutation in familial malignant melanoma in Southern Sweden. Cancer Res 1996; 56: 2497-2500.