期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 26, 期 1, 页码 88-96出版社
WILEY
DOI: 10.1111/pcmr.12032
关键词
melanoma; KIT; predisposition; nevus
资金
- Societe Francaise de Dermatologie
- Ligue contre le Cancer
- INCA
- Association Pour La Recherche Contre le Cancer (ARC)
- Fondo de Investigaciones Sanitarias (FIS) [05/0302, 06/0265, 09/1393]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR)
- GenoMEL Exchange Program fund by the European Commission under the 6th Framework Programme
As loss of KIT frequently occurs in melanoma progression, we hypothesized that KIT is implicated in predisposition to melanoma (MM). Thus, we sequenced the KIT coding region in 112 familial MM cases and 143 matched controls and genotyped tag single-nucleotide polymorphisms (SNPs) in two cohorts of melanoma patients and matched controls. Five rare KIT substitutions, all predicted possibly or probably deleterious, were identified in five patients, but none in controls [RR = 2.26 (1.26-2.26)]. Expressed in melanocyte lines, three substitutions inhibited KIT signaling. Comparison with exomes database (7020 alleles) confirmed a significant excess of rare deleterious KIT substitutions in patients. Additionally, a common SNP, rs2237028, was associated with MM risk, and 6 KIT variants were associated with nevus count. Our data strongly suggest that rare KIT substitutions predispose to melanoma and that common variants at KIT locus may also impact nevus count and melanoma risk.
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