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Genetic variation at KIT locus may predispose to melanoma
Agnes Bourillon1, Hui-Han Hu, Gilles Hetet
1Département de Génétique, Hôpital Bichat-Claude Bernard, APHP, Paris, France.
Pigment Cell & Melanoma Research
|October 2, 2012
Summary
Rare KIT gene variants significantly increase melanoma risk. These genetic changes, particularly substitutions, were found more often in melanoma patients, suggesting a predisposition role for KIT in this skin cancer.
Area of Science:
- Genetics
- Oncology
- Dermatology
Background:
- Loss of KIT function is common in melanoma progression.
- KIT signaling pathways are crucial in melanocyte development and function.
Purpose of the Study:
- To investigate the role of KIT gene variants in melanoma predisposition.
- To determine if rare KIT substitutions or common single-nucleotide polymorphisms (SNPs) are associated with melanoma risk or nevus count.
Main Methods:
- Sequencing of the KIT coding region in familial melanoma cases and controls.
- Genotyping of tag SNPs in independent melanoma patient cohorts.
- Functional analysis of KIT substitutions in melanocyte cell lines.
- Comparison with large exome databases.
Main Results:
- Five rare, deleterious KIT substitutions were identified in melanoma patients but not in controls (RR = 2.26).
- Three of these substitutions inhibited KIT signaling in melanocyte lines.
- A significant excess of rare deleterious KIT substitutions was observed in patients compared to exome databases.
- A common SNP (rs2237028) and six KIT variants were associated with melanoma risk and nevus count, respectively.
Conclusions:
- Rare KIT substitutions strongly predispose individuals to melanoma.
- Common variants in the KIT locus may also influence nevus count and melanoma susceptibility.
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