Genetic Analysis of Familial Melanoma

In collaboration with members of The International Melanoma Consortium, we propose to study melanoma in families lacking mutations in the cyclin-dependent kinase inhibitor 2 (CDKN2 or p16) gene, or the cyclin-dependant kinase 4 (CDK4). CDKN2 and CDK4 are both genes that encode presumed tumor suppressor genes, mutant forms of which are known to cause increased susceptibility to melanoma. The purpose of the present study then is to confirm the existence of and to identify additional gene(s) involved in heritable melanoma (cutaneous and ocular) and their precursor lesions (atypical nevi) by linkage analysis and gene mapping strategies. It is clear that the risk to develop atypical nevi and/or melanoma is strongly influenced by genetic and environmental factors (e.g. sun exposure). Characterization of such genes could provide important insights into the inheritance, pathogenesis, and treatment of this increasingly important disease.

Study Overview

• Status: Completed
• Conditions: Melanoma

Detailed Description

In collaboration with members of The International Melanoma Genetics Consortium, we propose to study melanoma in families lacking mutations in the cyclin-dependent kinase inhibitor 2 (CDKN2A), or the cyclin-dependant kinase 4 (CDK4) genes. CDKN2 and CDK4 are both genes that encode presumed tumor suppressor genes, mutant forms of which are known to cause increased susceptibility to melanoma. The purpose of the present study then is to confirm the existence of and to identify additional gene(s) involved in heritable melanoma (cutaneous and ocular) and their precursor lesions (atypical nevi) by linkage analysis and gene mapping strategies. It is clear that the risk to develop atypical nevi and/or melanoma is strongly influenced by genetic and environmental factors (e.g. sun exposure). Characterization of such genes could provide important insights into the inheritance, pathogenesis, and treatment of this increasingly important disease.

• Study Type: Observational
• Enrollment (Anticipated): 3000

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Human Genome Research Institute (NHGRI), 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• INCLUSION CRITERIA:

Inclusion into this study was restricted to families containing at least three CMM cases with DNA available for genotyping, and CDKN2A and CDK4 involvement and had been excluded.

All families must be mutation negative for both CDKN2A and CDK4.

This study will also include families with at least one case of ocular and two cases of other cutaneous melanomas, or at least 2 ocular melanomas (except where they occur in parent and child).

EXCLUSION CRITERIA:

Any family showing evidence of haplotype sharing in the 9p21-p22 region, where CDKN2A is located, was also excluded.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Human Genome Research Institute (NHGRI)

Publications and helpful links

General Publications

• Hussussian CJ, Struewing JP, Goldstein AM, Higgins PA, Ally DS, Sheahan MD, Clark WH Jr, Tucker MA, Dracopoli NC. Germline p16 mutations in familial melanoma. Nat Genet. 1994 Sep;8(1):15-21. doi: 10.1038/ng0994-15.
• Kamb A, Shattuck-Eidens D, Eeles R, Liu Q, Gruis NA, Ding W, Hussey C, Tran T, Miki Y, Weaver-Feldhaus J, et al. Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet. 1994 Sep;8(1):23-6. doi: 10.1038/ng0994-22.
• Hayward NK. The current situation with regard to human melanoma and genetic inferences. Curr Opin Oncol. 1996 Mar;8(2):136-42. doi: 10.1097/00001622-199603000-00011.

Study record dates

Study Major Dates

• Study Start: March 4, 1999
• Study Completion: March 7, 2011

Study Registration Dates

• First Submitted: June 19, 2006
• First Submitted That Met QC Criteria: June 19, 2006
• First Posted (Estimate): June 21, 2006

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 30, 2017
• Last Verified: March 7, 2011

More Information

Terms related to this study

• Keywords: Cancer; Linkage Analysis; Genotyping; Hereditary Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 999999012; OH99-HG-N012