Abstract
<div>Abstract<p><b>Purpose:</b><i>KIT</i> aberrations were described in acral and mucosal melanomas in largely Caucasian populations. Asian populations are more prone to develop acral and mucosal than cutaneous melanomas, and may harbor a high frequency of <i>KIT</i> aberrations.</p><p><b>Experimental Design:</b> Melanoma subtypes (<i>n</i> = 502) were analyzed histologically to determine melanoma subtype. Tissue samples were analyzed for mutations in exons 9, 11, 13, 17, and 18 of <i>KIT</i> gene in genomic DNA by PCR amplification and Sanger sequencing. The copy numbers of the <i>KIT</i> gene were analyzed by quantitative PCR, and protein expression levels of KIT (CD117) were determined by immunohistochemistry.</p><p><b>Results:</b> The most common melanoma subtypes were acral (38.4%) and mucosal (33.3%) melanomas in this population. The overall incidence of somatic mutations within the <i>KIT</i> gene was 10.8% (54/502), and all subtypes of melanoma contained <i>KIT</i> mutations. Increases in <i>KIT</i> gene copy numbers were correlated to CD117 overexpression. The genetic mutations of <i>KIT</i> were unrelated to the age, gender, stage, thickness, and ulceration of primary melanomas. Importantly, the overall survival of melanoma patients with <i>KIT</i> mutations (<i>P</i> = 0.001) or with <i>KIT</i> aberrations (mutation plus amplification, <i>P</i> = 0.0002) was significantly shorter than that of patients without such alterations.</p><p><b>Conclusion:</b> In China, the prevalent melanomas are acral and mucosal melanomas. <i>KIT</i> mutations are detected in all melanoma subtypes. Our study suggests that increases in <i>KIT</i> gene copy numbers, but not <i>KIT</i> mutations, may be correlated to CD117 overexpression. For the first time, our study suggests that genetic <i>KIT</i> aberration is an adverse prognostic factor for melanoma. <i>Clin Cancer Res; 17(7); 1684–91. ©2011 AACR</i>.</p></div>
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