Qin Yan Ru, Fu Li, Sham Pak C, Kwong Dora L W, Zhu Cai Lei, Chu Kevin K W, Li Yan, Guan Xin-Yuan
Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Int J Cancer. 2008 Aug 15;123(4):826-30. doi: 10.1002/ijc.23577.
Esophageal squamous cell carcinoma (ESCC) is one of the most common solid tumors in the world with poor prognosis. Deletion of chromosome 3p is one of the most frequent chromosomal alterations in ESCC, suggesting the existence of one or more tumor suppressor genes (TSGs) at this region. In the present study, a recently developed high-throughput and high-resolution technology, single-nucleotide polymorphism (SNP)-mass array, was applied to investigate loss of heterozygosity on 3p in 100 primary ESCC cases with 386 SNP markers. Four commonly deleted regions (CDRs) at 3p26.3, 3p22, 3p21.3 and 3p14.2 were identified. Absent and down-regulated expression of several candidate TSGs, including CHL1, PCAF, RBMS3, PLCD1 and CACNA2D3, were detected in primary ESCC tumors and ESCC cell lines. Moreover, deletions of CDRs 2 and 4 were correlated with advanced tumor stage and deletion of CDR2 was associated with tumor metastasis in ESCC. Our findings provided evidence that minimal deleted regions at 3p26.3, 3p22, 3p21.3 and 3p14.2 containing potential TSGs may contribute to the pathogenesis of esophageal cancer.
食管鳞状细胞癌（ESCC）是世界上最常见的实体瘤之一，预后较差。3号染色体短臂（3p）缺失是ESCC中最常见的染色体改变之一，提示该区域存在一个或多个肿瘤抑制基因（TSG）。在本研究中，一种最近开发的高通量、高分辨率技术，即单核苷酸多态性（SNP）-质谱分析，被应用于研究100例原发性ESCC病例中3p上的杂合性缺失，使用了386个SNP标记。在3p26.3、3p22、3p21.3和3p14.2处鉴定出四个常见缺失区域（CDR）。在原发性ESCC肿瘤和ESCC细胞系中检测到包括CHL1、PCAF、RBMS3、PLCD1和CACNA2D3在内的几个候选TSG的缺失和表达下调。此外，CDR2和CDR4的缺失与肿瘤晚期相关，CDR2的缺失与ESCC中的肿瘤转移相关。我们的研究结果提供了证据，表明在3p26.3、3p22、3p21.3和3p14.2处含有潜在TSG的最小缺失区域可能有助于食管癌的发病机制。
