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

为了评估7号染色体缺失在口腔鳞状细胞癌（SCC）进展中的作用，并确定假定的抑癌基因的精确定位，我们研究了35例无关的口腔SCC患者的肿瘤，通过聚合酶链反应（PCR）-杂合性缺失（洛）分析，使用14个不同的多态性位点。7号染色体上有55.9%的个体在一个或多个位点发生了等位基因丢失（洛）。在所检测的基因座中，常见的洛丢失发生在染色体7 q31，1的D 7S 522位点，测量范围在1cM以内。这些结果表明，7 q的洛缺失是口腔鳞癌发生和/或发展的一个常见事件，并提示在D 7S 522位点附近存在一个新的抑制基因，该基因可能在这些事件中发挥作用。采用差异显示技术和代表性差异分析方法，对D 7S 522位点附近的洛缺失（LOH）和非LOH的肿瘤进行分析，寻找可能在淋巴结转移中起作用的抑癌基因候选基因。分离出两个DNA片段，并确认其存在于染色体7 q上。经测序分析，推测该基因可能是一个与口腔鳞癌发生发展有关的抑癌基因。

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.