Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Aug;85(4):527–530. doi: 10.1054/bjoc.2001.1944

A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families

A M Goldstein 1, L Liu 2, M G Shennan 3, D Hogg 2,4, M A Tucker 1, J P Struewing 1
PMCID: PMC2364106  PMID: 11506491

Abstract

One of the most common melanoma-related CDKN2A mutations reported in North America is the V126D mutation. We examined nine markers surrounding CDKN2A in three American and four Canadian families carrying the V126D mutation. All seven families had a haplotype consistent with a common ancestor/founder for this mutation. In addition, the mutation appears to have originated 34–52 generations ago (1-LOD-unit support interval 13–98 generations). © 2001 Cancer Research Campaign http:///www.bjcancer.com

Keywords: melanoma, CDKN2A, V126D, founder

Full Text

The Full Text of this article is available as a PDF (48.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borg A., Johannsson U., Johannsson O., Häkansson S., Westerdahl J., Mäsbäck A., Olsson H., Ingvar C. Novel germline p16 mutation in familial malignant melanoma in southern Sweden. Cancer Res. 1996 Jun 1;56(11):2497–2500. [PubMed] [Google Scholar]
  2. Chin L., Merlino G., DePinho R. A. Malignant melanoma: modern black plague and genetic black box. Genes Dev. 1998 Nov 15;12(22):3467–3481. doi: 10.1101/gad.12.22.3467. [DOI] [PubMed] [Google Scholar]
  3. Ciotti P., Struewing J. P., Mantelli M., Chompret A., Avril M. F., Santi P. L., Tucker M. A., Bianchi-Scarrà G., Bressac-de Paillerets B., Goldstein A. M. A single genetic origin for the G101W CDKN2A mutation in 20 melanoma-prone families. Am J Hum Genet. 2000 Jun 22;67(2):311–319. doi: 10.1086/303001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ghiorzo P., Ciotti P., Mantelli M., Heouaine A., Queirolo P., Rainero M. L., Ferrari C., Santi P. L., De Marchi R., Farris A. Characterization of ligurian melanoma families and risk of occurrence of other neoplasia. Int J Cancer. 1999 Nov 12;83(4):441–448. doi: 10.1002/(sici)1097-0215(19991112)83:4<441::aid-ijc2>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  5. Goldstein A. M., Struewing J. P., Chidambaram A., Fraser M. C., Tucker M. A. Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations. J Natl Cancer Inst. 2000 Jun 21;92(12):1006–1010. doi: 10.1093/jnci/92.12.1006. [DOI] [PubMed] [Google Scholar]
  6. Gruis N. A., van der Velden P. A., Sandkuijl L. A., Prins D. E., Weaver-Feldhaus J., Kamb A., Bergman W., Frants R. R. Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds. Nat Genet. 1995 Jul;10(3):351–353. doi: 10.1038/ng0795-351. [DOI] [PubMed] [Google Scholar]
  7. Hussussian C. J., Struewing J. P., Goldstein A. M., Higgins P. A., Ally D. S., Sheahan M. D., Clark W. H., Jr, Tucker M. A., Dracopoli N. C. Germline p16 mutations in familial melanoma. Nat Genet. 1994 Sep;8(1):15–21. doi: 10.1038/ng0994-15. [DOI] [PubMed] [Google Scholar]
  8. Kefford R. F., Newton Bishop J. A., Bergman W., Tucker M. A. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: A consensus statement of the Melanoma Genetics Consortium. J Clin Oncol. 1999 Oct;17(10):3245–3251. doi: 10.1200/JCO.1999.17.10.3245. [DOI] [PubMed] [Google Scholar]
  9. 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. Nat Genet. 1999 Jan;21(1):128–132. doi: 10.1038/5082. [DOI] [PubMed] [Google Scholar]
  10. MacKie R. M., Andrew N., Lanyon W. G., Connor J. M. CDKN2A germline mutations in U.K. patients with familial melanoma and multiple primary melanomas. J Invest Dermatol. 1998 Aug;111(2):269–272. doi: 10.1046/j.1523-1747.1998.00267.x. [DOI] [PubMed] [Google Scholar]
  11. Neuhausen S. L., Godwin A. K., Gershoni-Baruch R., Schubert E., Garber J., Stoppa-Lyonnet D., Olah E., Csokay B., Serova O., Lalloo F. Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study. Am J Hum Genet. 1998 Jun;62(6):1381–1388. doi: 10.1086/301885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Neuhausen S. L., Mazoyer S., Friedman L., Stratton M., Offit K., Caligo A., Tomlinson G., Cannon-Albright L., Bishop T., Kelsell D. Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study. Am J Hum Genet. 1996 Feb;58(2):271–280. [PMC free article] [PubMed] [Google Scholar]
  13. Newton Bishop J. A., Harland M., Bennett D. C., Bataille V., Goldstein A. M., Tucker M. A., Ponder B. A., Cuzick J., Selby P., Bishop D. T. Mutation testing in melanoma families: INK4A, CDK4 and INK4D. Br J Cancer. 1999 Apr;80(1-2):295–300. doi: 10.1038/sj.bjc.6690354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Parry D., Peters G. Temperature-sensitive mutants of p16CDKN2 associated with familial melanoma. Mol Cell Biol. 1996 Jul;16(7):3844–3852. doi: 10.1128/mcb.16.7.3844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pollock P. M., Spurr N., Bishop T., Newton-Bishop J., Gruis N., van der Velden P. A., Goldstein A. M., Tucker M. A., Foulkes W. D., Barnhill R. Haplotype analysis of two recurrent CDKN2A mutations in 10 melanoma families: evidence for common founders and independent mutations. Hum Mutat. 1998;11(6):424–431. doi: 10.1002/(SICI)1098-1004(1998)11:6<424::AID-HUMU2>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  16. Pomerantz J., Schreiber-Agus N., Liégeois N. J., Silverman A., Alland L., Chin L., Potes J., Chen K., Orlow I., Lee H. W. The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell. 1998 Mar 20;92(6):713–723. doi: 10.1016/s0092-8674(00)81400-2. [DOI] [PubMed] [Google Scholar]
  17. Ranade K., Hussussian C. J., Sikorski R. S., Varmus H. E., Goldstein A. M., Tucker M. A., Serrano M., Hannon G. J., Beach D., Dracopoli N. C. Mutations associated with familial melanoma impair p16INK4 function. Nat Genet. 1995 May;10(1):114–116. doi: 10.1038/ng0595-114. [DOI] [PubMed] [Google Scholar]
  18. Randerson-Moor J. A., Harland M., Williams S., Cuthbert-Heavens D., Sheridan E., Aveyard J., Sibley K., Whitaker L., Knowles M., Bishop J. N. A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family. Hum Mol Genet. 2001 Jan 1;10(1):55–62. doi: 10.1093/hmg/10.1.55. [DOI] [PubMed] [Google Scholar]
  19. Ruiz A., Puig S., Malvehy J., Lázaro C., Lynch M., Gimenez-Arnau A. M., Puig L., Sánchez-Conejo J., Estivill X., Castel T. CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia. J Med Genet. 1999 Jun;36(6):490–493. [PMC free article] [PubMed] [Google Scholar]
  20. Serrano M., Gómez-Lahoz E., DePinho R. A., Beach D., Bar-Sagi D. Inhibition of ras-induced proliferation and cellular transformation by p16INK4. Science. 1995 Jan 13;267(5195):249–252. doi: 10.1126/science.7809631. [DOI] [PubMed] [Google Scholar]
  21. Serrano M., Hannon G. J., Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993 Dec 16;366(6456):704–707. doi: 10.1038/366704a0. [DOI] [PubMed] [Google Scholar]
  22. Soufir N., Avril M. F., Chompret A., Demenais F., Bombled J., Spatz A., Stoppa-Lyonnet D., Bénard J., Bressac-de Paillerets B. Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group. Hum Mol Genet. 1998 Feb;7(2):209–216. doi: 10.1093/hmg/7.2.209. [DOI] [PubMed] [Google Scholar]
  23. Zhang Y., Xiong Y., Yarbrough W. G. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell. 1998 Mar 20;92(6):725–734. doi: 10.1016/s0092-8674(00)81401-4. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES