Isolation of a novel tumor suppressor gene on the Chromosome 7 associated with oral squamous cell carcinoma.

为了评价7号染色体缺失在口腔鳞状细胞癌(SCC)进展中的作用，并确定可能的抑癌基因的精确定位，我们利用14个不同的多态基因座，采用聚合酶链式反应(PCR)-杂合性缺失(LOH)分析方法，对35例口腔鳞癌患者的肿瘤进行了研究。在一个或多个基因座发现55.9%的7号染色体等位基因丢失。在所检测的基因座中，频繁杂合性缺失发生在染色体7q31，1上的D7S522上，发生频率LOH的范围在1 cM以内。这些结果表明，7q的LOH是口腔鳞状细胞癌发生和/或发展过程中的常见事件，并提示D7S522基因附近存在一个新的抑制基因，该基因可能在这些事件中起作用。采用差异显示法和代表性差异分析方法，以D7S522基因座有无杂合性缺失的肿瘤为研究对象，寻找在淋巴结转移中可能起作用的抑癌基因候选基因。分离到两个DNA片段，证实存在于7q染色体上。这些DNA片段的序列被认为是参与口腔鳞状细胞癌发生发展的抑癌基因的一部分。

To evaluate the role of chromosome 7 deletions in oral squamous cell carcinoma (SCC) progression and to define the precise localization of putative tumor suppressor genes, we studied tumors from 35 unrelated patients with oral SCC by the polymerase chain reaction (PCR)-loss of heterozygosity (LOH) assay, using 14 different polymorphic loci. Chromosome 7 allelic losses (LOH) were observed in 55.9% at one or more loci. Among the loci tested, frequent LOH was restricted at D7S522 on chromosome 7q31,1, which was measured within 1 cM. These results indicate that LOH of 7q is a common event in oncogenesis and/or progression of oral SCC, and also suggest the existence of a new suppressor gene near D7S522 locus, which may play a role in these events. To identify the candidate gene for the tumor suppressor gene near D7S522 locus, which may play a role in lymph node metastasis, differential display method and representational difference analysis, using tumors with and without LOH at this locus. Two DNA fragments was isolated and confirmed the presence on chromosome 7q. The sequences of the DNA fragments were detected and they were considered as a part of a putative tumor suppressor gene involved in the carcinogenesis and development of oral squamous cell carcinoma.