Melanoma hereditary predisposition in Uruguayan families
Preliminary results
Keywords:
MELANOMA, HEREDITARY NEOPLASTIC SYNDROMES, MUTATION, URUGUAYAbstract
Cutaneous melanoma is the cancer whose incidence has the highest growing rates worldwide. Mortality rates have not decreased in spite of diagnostic and management therapies. There are two expressions of melanoma: sporadic and hereditary forms. The latest include persons with high risk to develop melanoma, whose frequency varies according to the studied population. The aim of this study is to analyze hereditary predisposition of melanoma in Uruguay. Fourteen families with high risk of hereditary melanoma were identified using a sift questionnaire. Search for germline mutations in CDKN2A and CDK4 was performed in 17 patients of these families who gave informed consent using PCR-SSCP (Polymerase Chain Reaction - Single Stranded Conformational Polymorphism). Fragments with atypical SSCP patterns were analyzed by sequenciation. Two mutations were identified; the first mutation in exon 2 of CDKN2A (E88X) in two first-degree relatives carriers of multiple melanomas and familial syndrome of atypical nevus (SFNA) with familial history of melanoma and pancreatic cancer (this germinal mutation has not been described in families with melanoma) and the second mutation (G101W) is one of the most frequent worldwide. Both mutations were identified in patients with SFNA and multiple melanoma within families. The frequency of these mutations is the same as reported in previous studies with similar selection criteria.
References
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(32) Laud K, Kannengiesser C, Avril MF, Chompret A, Stoppa-Lyonnet D, Desjardins L, et al. French Herediatary Melanoma Study Group. BRAF as a melanoma susceptibility candidate gene? Cancer Res 2003; 63: 3061-5.
(33) Meyer P, Klaes R, Schmitt C, Boettger MB, Garbe C. Exclusion of BRAFV599E as a melanoma susceptibility mutation. Int J Cancer 2003; 106: 78-80.
(34) de Snoo FA, Bergman W, Gruis NA. Familial melanoma: a complex disorder leading to controversy on DNA testing. Fam Cancer 2003; 2: 109-16.
(35) Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility. Adopted on February 20, 1996. J Clin Oncol 1996; 14: 1730-6.
(36) Tsao H, Niendorf K. Genetic testing in hereditary melanoma. J Am Acad Dermatol 2004; 51: 803-8.
(37) Marsh D, Zori R. Genetic insights into familial cancers: update and recent discoveries. Cancer Lett 2002; 181: 125-64.
(38) Ferrone CR, Ben Porat L, Panageas KS, Berwick M, Halpern AC, Patel A, et al. Clinicopathological features of and risk factors for multiple primary melanomas. JAMA 2005; 294: 1647-54.
(39) Puig S, Malvehy J, Badenas C, Ruiz A, Jimenez D, Cuellar F, et al. Role of the CDKN2A locus in patients with multiple primary melanomas. J Clin Oncol 2005; 23: 3043-51.
(40) Delgado L, Fernández G, González A, Bressac-de Paillerets B, Gualco G, Bombled J, et al. Hereditary breast cancer associated with a germline BRCA2 mutation in identical female twins with similar disease expression. Cancer Genet Cytogenet 2002; 133: 24-8.
(41) Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 1989; 86: 2766-70.
(42) Ciotti P, Struewing JP, Mantelli M, Chompret A, Avril MF, Santi PL, et al. A single genetic origin for the G101W CDKN2A mutation in 20 melanoma-prone families. Am J Hum Genet 2000; 67: 311-9.
(43) Levanat S, Situm M, Crnic I, Marasovic D, Puizina-Ivic N, Pokupcic N, et al. Alterations in CDKN2A locus as potential indicator of melanoma predisposition in relatives of non-familial melanoma cases. Croat Med J 2003; 44: 418-24.
(44) Huber J, Ramos ES. The P48T germline mutation and polymorphism in the CDKN2A gene of patients with melanoma. Braz J Med Biol Res 2006; 39: 237-41.
(45) Eliason MJ, Larson AA, Florell SR, Zone JJ, Cannon-Albright LA, Samlowski WE, et al. Population-based prevalence of CDKN2A mutations in Utah melanoma families. J Invest Dermatol 2006; 126: 660-6.
(2) Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. CA Cancer J Clin 1999; 49: 8-31.
(3) Diepgen TL, Mahler V. The epidemiology of skin cancer. Br J Dermatol 2002; 146 (Suppl 61): 1-6.
(4) Barrios E, Vasallo J, De Stéfani E. Patterns of cutaneous malignant melanoma incidence and mortality in Uruguay. Melanoma Res 2001; 11(Suppl 1): S138.
(5) Priario J. Historia del melanoma maligno en Uruguay. Rev med Urug 2005; 21: 255-68.
(6) Kraehn M, Schartl M, Peter R. Human melanoma: a genetic disease? Cancer 1994; 75: 1228-37.
(7) MacKie RM. Incidence, risk factors and prevention of melanoma. Eur J Cancer 1998; 34 (Suppl 3): S3-S6.
(8) Greene M. The genetics of hereditary melanoma and nevi. 1998 update. Cancer 1999; 86: 2464-77.
(9) Goldstein AM, Tucker MA. Genetic epidemiology of familial melanoma. Dermatol Clin 1995; 13: 605-12.
(10) Aitken JF, Duffy DL, Green A, Youl P, MacLennan R, Martin NG. Heterogeneity of melanoma risk in families of melanoma patients. Am J Epidemiol 1994; 140:961-73.
(11) Slade J, Marghoob AA, Salopek TG, Rigel DS, Kopf AW, Bart RS. Atypical mole syndrome: risk factor for cutaneous malignant melanoma and implications for management. J Am Acad Dermatol 1995; 32: 479-94.
(12) Aitken J, Welch J, Duffy D, Milligan A, Green A, Martin N, et al. CDKN2A variants in a population-based sample of Queensland families with melanoma. J Natl Cancer Inst 1999; 91: 446-52.
(13) Holland EA, Schmid H, Kefford RF, Mann GJ. CDKN2A (P16(INK4a)) and CDK4 mutation analysis in 131 Australian melanoma probands: effect of family history and multiple primary melanomas. Genes Chromosomes Cancer 1999; 25: 339-48.
(14) Hashemi J, Platz A, Ueno T, Stierner U, Ringborg U, Hansson J. CDKN2A germ-line mutations in individuals with multiple cutaneous melanomas. Cancer Res 2000; 60: 6864-7.
(15) Soufir N, Avril MF, Chompret A, Demenais F, Bombled J, Spatz A, et al. Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group. Hum Mol Genet 1998; 7: 209-16.
(16) Newton Bishop JA, Harland M, Bennett DC, Bataille V, Goldstein AM, Tucker MA, et al. Mutation testing in melanoma families: INK4A, CDK4 and INK4D. Br J Cancer 1999; 80: 295-300.
(17) Landi MT, Goldstein AM, Tsang S, Munroe D, Modi W, Ter-Minassian M, et al. Genetic susceptibility in familial melanoma from northeastern Italy. J Med Genet 2004; 41: 557-66.
(18) Fraser MC, Goldstein AM, Tucker MA. The genetics of melanoma. Semin Oncol Nurs 1997; 13: 108-14.
(19) Sauroja I, Smeds J, Vlaykova T, Kumar R, Talve L, Hahka-Kemppinen M, et al. Analysis of G(1)/S checkpoint regulators in metastatic melanoma. Genes Chromosomes Cancer 2000; 28: 404-14.
(20) Nam J. Interval estimation and significance testing for cyclic trends in seasonality studies. Biometrics 1995; 51: 1411-7.
(21) Zuo L, Weger J, Yang Q, Goldstein AM, Tucker MA, Walker GJ, et al. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet 1996; 12: 97-9.
(22) Cannon-Albright LA, Goldgar DE, Meyer LJ, Lewis CM, Anderson DE, Fountain JW, et al. Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22. Science 1992; 258: 1148-52.
(23) Plna K, Hemminki K. Re: High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst 2001; 93(4): 323-5.
(24) Borg A, Sandberg T, Nilsson K, Johannsson O, Klinker M, Masback A, et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst 2000; 92: 1260-6.
(25) Lynch HT, Brand RE, Hogg D, Deters CA, Fusaro RM, Lynch JF, et al. Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: the familial atypical mole melanoma-pancreatic carcinoma syndrome. Cancer 2002; 94: 84-96.
(26) Goldstein AM, Chidambaram A, Halpern A, Holly EA, Guerry IV D, Sagebiel R, et al. Rarity of CDK4 germline mutations in familial melanoma. Melanoma Res 2002; 12: 51-5.
(27) Pollock PM, Stark MS, Palmer JM, Walters MK, Aitken JF, Martin NG, et al. Mutation analysis of the CDKN2A promoter in Australian melanoma families. Genes Chromosomes Cancer 2001; 32: 89-94.
(28) Aitken JF, Green A, MacLennan R, Jackman L, Martin NG. Comparability of surrogate and self-reported information on melanoma risk factors. Br J Cancer 1993; 67: 1036-41.
(29) Goldstein AM, Struewing JP, Chidambaram A, Fraser MC, Tucker MA. Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations. J Natl Cancer Inst 2000; 92: 1006-10.
(30) Vasen HF, Gruis NA, Frants RR, van Der Velden PA, Hille ET, Bergman W. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16(p16-Leiden). Int J Cancer 2000; 87: 809-11.
(31) Battistutta D, Palmer J, Walters M, Walker G, Nancarrow D, Hayward N. Incidence of familial melanoma and MLM2 gene. Lancet 1994; 344: 1607-8.
(32) Laud K, Kannengiesser C, Avril MF, Chompret A, Stoppa-Lyonnet D, Desjardins L, et al. French Herediatary Melanoma Study Group. BRAF as a melanoma susceptibility candidate gene? Cancer Res 2003; 63: 3061-5.
(33) Meyer P, Klaes R, Schmitt C, Boettger MB, Garbe C. Exclusion of BRAFV599E as a melanoma susceptibility mutation. Int J Cancer 2003; 106: 78-80.
(34) de Snoo FA, Bergman W, Gruis NA. Familial melanoma: a complex disorder leading to controversy on DNA testing. Fam Cancer 2003; 2: 109-16.
(35) Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility. Adopted on February 20, 1996. J Clin Oncol 1996; 14: 1730-6.
(36) Tsao H, Niendorf K. Genetic testing in hereditary melanoma. J Am Acad Dermatol 2004; 51: 803-8.
(37) Marsh D, Zori R. Genetic insights into familial cancers: update and recent discoveries. Cancer Lett 2002; 181: 125-64.
(38) Ferrone CR, Ben Porat L, Panageas KS, Berwick M, Halpern AC, Patel A, et al. Clinicopathological features of and risk factors for multiple primary melanomas. JAMA 2005; 294: 1647-54.
(39) Puig S, Malvehy J, Badenas C, Ruiz A, Jimenez D, Cuellar F, et al. Role of the CDKN2A locus in patients with multiple primary melanomas. J Clin Oncol 2005; 23: 3043-51.
(40) Delgado L, Fernández G, González A, Bressac-de Paillerets B, Gualco G, Bombled J, et al. Hereditary breast cancer associated with a germline BRCA2 mutation in identical female twins with similar disease expression. Cancer Genet Cytogenet 2002; 133: 24-8.
(41) Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 1989; 86: 2766-70.
(42) Ciotti P, Struewing JP, Mantelli M, Chompret A, Avril MF, Santi PL, et al. A single genetic origin for the G101W CDKN2A mutation in 20 melanoma-prone families. Am J Hum Genet 2000; 67: 311-9.
(43) Levanat S, Situm M, Crnic I, Marasovic D, Puizina-Ivic N, Pokupcic N, et al. Alterations in CDKN2A locus as potential indicator of melanoma predisposition in relatives of non-familial melanoma cases. Croat Med J 2003; 44: 418-24.
(44) Huber J, Ramos ES. The P48T germline mutation and polymorphism in the CDKN2A gene of patients with melanoma. Braz J Med Biol Res 2006; 39: 237-41.
(45) Eliason MJ, Larson AA, Florell SR, Zone JJ, Cannon-Albright LA, Samlowski WE, et al. Population-based prevalence of CDKN2A mutations in Utah melanoma families. J Invest Dermatol 2006; 126: 660-6.
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2007-06-30
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Larre Borges García A, Scarone M, Delgado L, Núñez J, Laporte M, Fernández G, et al. Melanoma hereditary predisposition in Uruguayan families: Preliminary results. Rev. Méd. Urug. [Internet]. 2007 Jun. 30 [cited 2024 Nov. 21];23(2):109-15. Available from: https://revista.rmu.org.uy/index.php/rmu/article/view/625
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