Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, DHHS, MD, USA.
Pigment Cell Melanoma Res. 2012 Mar;25(2):243-7. doi: 10.1111/j.1755-148X.2012.00969.x. Epub 2012 Jan 23.
Copy number variations (CNVs) have been shown to contribute substantially to disease susceptibility in several inherited diseases including cancer. We conducted a genome-wide search for CNVs in blood-derived DNA from 79 individuals (62 melanoma patients and 17 spouse controls) of 30 high-risk melanoma-prone families without known segregating mutations using genome-wide comparative genomic hybridization (CGH) tiling arrays. We identified a duplicated region on chromosome 4q13 in germline DNA of all melanoma patients in a melanoma-prone family with three affected siblings. We confirmed the duplication using quantitative PCR and a custom-made CGH array design spanning the 4q13 region. The duplicated region contains 10 genes, most of which encode CXC chemokines. Among them, CXCL1 (melanoma growth-stimulating activity α) and IL8 (interleukin 8) have been shown to stimulate melanoma growth in vitro and in vivo. Our data suggest that the alteration of CXC chemokine genes may confer susceptibility to melanoma.
拷贝数变异（CNVs）已被证明在包括癌症在内的几种遗传性疾病中对疾病易感性有很大的贡献。我们使用全基因组比较基因组杂交（CGH）平铺阵列，对 30 个高风险黑色素瘤易感家族中 79 名个体（62 名黑色素瘤患者和 17 名配偶对照）的血液衍生 DNA 进行了全基因组范围内的 CNV 搜索。我们在一个有三个受影响兄弟姐妹的黑色素瘤易感家族的所有黑色素瘤患者的种系 DNA 中发现了 4q13 染色体上的一个重复区域。我们使用定量 PCR 和跨越 4q13 区域的定制 CGH 阵列设计来证实重复。重复区域包含 10 个基因，其中大多数编码 CXC 趋化因子。其中，CXCL1（黑色素瘤生长刺激活性α）和 IL8（白细胞介素 8）已被证明可在体外和体内刺激黑色素瘤生长。我们的数据表明，CXC 趋化因子基因的改变可能导致黑色素瘤易感性。
