Mutation screening of CHD5 in melanoma-prone families linked to 1p36 revealed no deleterious coding or splice site changes

BACKGROUND: A subset of cutaneous malignant melanoma and dysplastic nevi (CMM/DN) families is linked to 1p36. To date, no CMM/DN susceptibility gene has been identified at this locus. Data from mouse studies identified chromodomain helicase DNA binding protein 5 (CHD5) as a tumor suppressor affecting cellular proliferation and apoptosis via the CDKN2A/p53 pathway. Based on these findings, we felt it was important to screen CHD5 as a familial CMM/DN susceptibility gene. METHODS: Eight unrelated CMM/DN families showing prior evidence of linkage to the 1p36 locus were identified for CHD5 mutation screening. One CMM/DN affected and one unaffected individual from each family were selected for sequencing of the CHD5 coding exons and their respective intron-exon boundaries. CHD5 variants that were identified solely among affecteds in the screening panel were further assessed by sequencing additional affected and unaffected members of these families to determine if the variant co-segregated with the CMM/DN phenotype. RESULTS: Single nucleotide polymorphisms in the CHD5 intronic and coding regions were identified among affecteds in the screening panel. None of these variants completely co-segregated with CMM/DN affection status among these eight families. CONCLUSION: There is no evidence to support CHD5 as a major melanoma susceptibility gene among the eight CMM/DN families screened.