Genetic Analysis of Familial Melanoma

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.

- 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.