Exomic Sequencing to Identify Germline Variants in Familial Melanoma.

Germlines are the source of DNA in all cells. A mutation at the germline level is the first step to developing cancer, and the vast majority of cancer is genetic. Melanoma, the leading cause of skin cancer death, is known to be highly heritable and rare. Using a family model, high risk variants related to melanoma can be identified. The goal of the study is to integrate information from sequencing, epigenetics, and expression to identify functional and regulatory genes that are associated with melanoma. Families with two or more 1st degree relatives with melanoma were considered at high risk and were investigated in this study. Initially, sequencing data of families with 3 or more relatives with the disease were examined and shared DNA variants were selected for further examination. Genetic databases and annotation tools were used to identify genes based on their known gene function and regulation, pathways, and variant conservation. Gene browsers were also used to identify any histone markers, DNA methylation sites, and other epigenetic indicators. Based on our candidate genes, there is a possibility of genetic heterogeneity, in which multiple genes may be responsible for disease susceptibility. Selected candidate genes will undergo fine mapping to further investigate the region and replication in additional families and population studies of melanoma.