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

为了评估第7号染色体缺失在口腔鳞状细胞癌（SCC）进展中的作用，并确定推定的肿瘤抑制基因的精确定位，我们使用14个不同的多态性位点，采用聚合酶链反应(PCR)-杂合性缺失（LOH）试验研究了35例无关口腔鳞状细胞癌患者的肿瘤。7号染色体1个或多个位点等位基因缺失（LOH）占55.9%。在检测的位点中，频繁LOH限制在染色体7q31,1上的D7S522，测量范围在1 cM以内。这些结果表明，7q的LOH是口腔鳞状细胞癌发生和/或进展中的一个常见事件，同时也提示在D7S522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起作用。为寻找可能在淋巴结转移中起作用的肿瘤抑制基因D7S522位点附近的候选基因，采用该位点有LOH和无LOH肿瘤的差异显示法和代表性差异分析。两个DNA片段被分离出来并证实存在于染色体7q上。DNA片段的序列被检测到，它们被认为是一个推定的肿瘤抑制基因的一部分，参与了口腔鳞状细胞癌的发生和发展。

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.