Genetic variation at KIT locus may predispose to melanoma |
| |
Authors: | Agnes Bourillon Hui‐Han Hu Gilles Hetet Jean‐Jacques Lacapere Jocelyne André Vincent Descamps Nicole Basset‐Seguin Zighereda Ogbah Susana Puig Philippe Saiag Martine Bagot Armand Bensussan Bernard Grandchamp Nicolas Dumaz Nadem Soufir |
| |
Affiliation: | 1. Département de Génétique, H?pital Bichat‐Claude Bernard, APHP, , Paris, France;2. Université Paris Diderot, Sorbonne Paris Cité, , Paris, France;3. INSERM U976, , Paris, France;4. INSERM U410, UFR Xavier Bichat, , Paris, France;5. Service de Dermatologie, H?pital Bichat Claude Bernard, APHP, , Paris, France;6. Service de Dermatologie, H?pital Saint Louis, APHP, , Paris, France;7. Melanoma Unit, Department of Dermatology Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, , Barcelona, Spain;8. Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, , Barcelona, Spain;9. Service de Dermatologie, H?pital Ambroise Paré, APHP, , Boulogne Billancourt, France |
| |
Abstract: | 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. |
| |
Keywords: | melanoma
KIT
predisposition nevus |
|
|