Large-Scale Analysis of KIT Aberrations in Chinese Patients with Melanoma
Large-Scale Analysis of KIT Aberrations in Chinese Patients with Melanoma
复制标题
中国黑色素瘤患者 KIT 畸变的大规模分析
DOI：
10.1158/1078-0432.ccr-10-2346
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发表时间：
2011-04-01
影响因子：
11.5
通讯作者：
Guo, Jun
中科院分区：
文献类型：
--
作者：
Kong, Yan;Si, Lu;Guo, Jun
目的：KIT畸变描述在肢端和粘膜黑色素瘤在大部分高加索人群。亚洲人群比皮肤人群更容易发生肢端和粘膜黑色素瘤，并且可能具有高频率的KIT畸变。实验设计：对502例黑色素瘤亚型进行组织学分析，确定黑色素瘤亚型。通过PCR扩增和Sanger测序分析组织样本基因组DNA中KIT基因外显子9、11、13、17和18的突变。定量PCR分析KIT基因拷贝数，免疫组化检测KIT （CD117）蛋白表达水平。结果：该人群中最常见的黑色素瘤亚型是肢端黑色素瘤（38.4%）和粘膜黑色素瘤（33.3%）。KIT基因内体细胞突变的总体发生率为10.8%(54/502)，所有黑色素瘤亚型均含有KIT突变。KIT基因拷贝数的增加与CD117过表达相关。KIT基因突变与原发性黑色素瘤的年龄、性别、分期、厚度、溃疡程度无关。重要的是，KIT突变（P = 0.001）或KIT畸变（突变加扩增，P = 0.0002）的黑色素瘤患者的总生存期明显短于没有这种改变的患者。结论：在中国，常见的黑色素瘤是肢端和粘膜黑色素瘤。KIT突变可在所有黑色素瘤亚型中检测到。我们的研究表明，KIT基因拷贝数的增加，而不是KIT突变，可能与CD117过表达相关。我们的研究首次表明，基因KIT畸变是黑色素瘤的不良预后因素。临床癌症研究；17 (7);1684 - 91。AACR©2011。
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 = 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 = 0.001) or with KIT aberrations (mutation plus amplification, P = 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. ©2011 AACR.