Large-Scale Analysis of KIT Aberrations in Chinese Patients with Melanoma

Abstract

Purpose: KIT 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 KIT aberrations.Experimental Design: Melanoma subtypes (n ¼ 502) were analyzed histologically to determine melanoma subtype. Tissue samples were analyzed for mutations in exons 9, 11, 13, 17, and 18 of KIT gene in genomic DNA by PCR amplification and Sanger sequencing. The copy numbers of the KIT gene were analyzed by quantitative PCR, and protein expression levels of KIT (CD117) were determined by immunohistochemistry.Results: 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 KIT gene was 10.8% (54/502), and all subtypes of melanoma contained KIT mutations. Increases in KIT gene copy numbers were correlated to CD117 overexpression. The genetic mutations of KIT were unrelated to the age, gender, stage, thickness, and ulceration of primary melanomas. Importantly, the overall survival of melanoma patients with KIT mutations (P ¼ 0.001) or with KIT aberrations (mutation plus amplification, P ¼ 0.0002) was significantly shorter than that of patients without such alterations.Conclusion: In China, the prevalent melanomas are acral and mucosal melanomas. KIT mutations are detected in all melanoma subtypes. Our study suggests that increases in KIT gene copy numbers, but not KIT mutations, may be correlated to CD117 overexpression. For the first time, our study suggests that genetic KIT aberration is an adverse prognostic factor for melanoma. Clin Cancer Res; 17(7); 1684-91. Ó2011 AACR.

Phase II Trial of Nilotinib in Patients With Metastatic Malignant Melanoma Harboring KIT Gene Aberration: A Multicenter Trial of Korean Cancer Study Group (UN10-06)

“…In our previous study, increased KIT copy number and KIT mutations were identified in approximately 30% and 7.6% of Chinese melanoma patients, respectively [8]. KIT mutations were detected in 20.7% of CSD, 11.9% of acral, and 9.6% of mucosal melanomas in a Chinese patient cohort (n 5 502) [9].…”

Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal

“…Although the precise reasons for lack of correlation between genetic sequencing and c-KIT immunohistochemical expression are not clear, ours is not the first study to note lack of correlation. 36,37 We recently observed a poor correlation between CD117 staining and c-KIT sequencing in atypical acral nevi. 38 Briefly, we noted that CD117 stained 80% of acral nevi (with and without atypia), but genomic analyses of KIT exon regions 11, 13 and 17 revealed no abnormalities in 'hotspots' frequently associated with point mutations in acral melanomas.…”

Targeted agents and immunotherapies: optimizing outcomes in melanoma

“…These alterations are disproportionately found in acral and mucosal melanomas, being present in ~10% of these less-common forms of melanoma 18 . Among the well-described tumour-suppressor genes, CDKN2A mutation is detected in ~50% of advanced-stage melanomas, and can rarely overlap with PTEN deletion (FIG.…”