Altered transcriptome signature of phenotypically normal skin fibroblasts heterozygous for CDKN2A in familial melanoma: relevance to early intervention.

ABSTRACT: Familial melanoma (FM) is a dominantly heritable cancer that is associated with mutations in the tumor suppressor CDKN2A/p16. In FM, a single inherited "hit" occurs in every somatic cell, enabling interrogation of cultured normal skin fibroblasts (SFs) from FM gene carriers as surrogates for the cell of tumor origin, namely the melanocyte. We compared the gene expression profile of SFs from FM individuals with two distinct CDKN2A/p16 mutations (V126D-p16 and R87P-p16) with the gene expression profile of SFs from age-matched individuals without p16 mutations and with no family history of melanoma. We show an altered transcriptome signature in normal SFs bearing a single-hit inherited mutation in the CDKN2A/p16 gene, wherein some of these abnormal alterations recapitulate changes observed in

SUBMITTER: Fan M 

PROVIDER: S-EPMC3702213 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature