Genetic variation at KIT locus may predispose to melanoma. (23rd November 2012)

• Record Type: Journal Article
• Authors: Bourillon, Agnes; Hu, Hui‐Han; Hetet, Gilles; Lacapere, Jean‐Jacques; André, Jocelyne; Descamps, Vincent; Basset‐Seguin, Nicole; Ogbah, Zighereda; Puig, Susana; Saiag, Philippe; Bagot, Martine; Bensussan, Armand; Grandchamp, Bernard; Dumaz, Nicolas; Soufir, Nadem
• Is Part Of: Pigment cell & melanoma research. Volume 26:Number 1(2013:Jan.)
• Page Start: 88
• Page End: 96
• Publication Date: 2012-11-23
• Subjects: Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12032
• Languages: English
• ISSNs: 1755-1471

Abstract

<abstract abstract-type="main" id="pcmr12032-abs-0001"> <title>Summary</title> <p>As loss of KIT frequently occurs in melanoma progression, we hypothesized that <italic>KIT</italic> is implicated in predisposition to melanoma (MM). Thus, we sequenced the <italic>KIT</italic> 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 <italic>KIT</italic> 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 <italic>KIT</italic> substitutions in patients. Additionally, a common SNP, rs2237028, was associated with MM risk, and 6 <italic>KIT</italic> variants were associated with nevus count. Our data strongly suggest that rare <italic>KIT</italic> substitutions predispose to melanoma and that common variants at <italic>KIT</italic> locus may also impact nevus count and melanoma risk.</p> </abstract>