抑癌基因PTEN在胃癌及癌前病变中的缺失和突变

Depletion and Mutation of Anti-oncogene PTEN in Gastric Cancer and Precancerous Lesions

目的:探讨胃癌及癌前病变中抑癌基因PTEN的缺失和突变。方法:收集中国医科大学2001～2002年胃镜中心活检标本,萎缩性胃炎、肠上皮化生、不典型增生及对应的正常胃粘膜各30例,收集同期肿瘤外科术后大体标本,早期胃癌及进展期胃癌各30例,饱和氯化钠法提取组织DNA,PCR-SSCP变性聚丙烯酰氨凝胶电泳银染法检测PTEN杂合性缺失(LOH),PCR-SSCP测序法检测PTEN基因突变。结果:在胃癌癌前期病变萎缩性胃炎、肠上皮化生、不典型增生中,PTEN的杂合性缺失率分别为10%、10%、13.3%,在早期胃癌中,PTEN的杂合性缺失率为20%,进展期胃癌中PTEN的杂合性缺失率为33.3%,而PTEN基因突变在癌前期病变及早期胃癌中无1例出现,在进展期胃癌中出现比率为10%,而且所有发生PTEN基因突变的病例均为LOH阳性病例。结论:PTEN基因缺失或失活与胃癌的浸润和转移的关系更密切。

Objective: To investigate the depletion and mutation of the anti-oncogene PTEN in gastric cancer and precancerous lesions. Methods: Thirty cases of normal gastric mucosa, precancerous lesions and gastric cancer were analyzed for PTEN loss of heterozygosity (LOH) and mutations within the entire coding region of the PTEN gene, DNA from the above group were extracted by the method of saturated sodium chloride, PTEN LOH was detected by PCR-SSCP denaturing PAGE gel electrophoresis and silver staining, PTEN mutation was detected via PCR-SSCP sequencing. Results: PTEN LOH was found in 10% of atrophic gastritis, 10% of intestinal metaplasia, 13.3% of atypical hyperplasia, 20% of early stage gastric cancer and 33.3% of advanced stage gastric cancer. None of the precancerous lesions and early stage gastric cancer showed PTEN mutations. For the advanced stage gastric cancer, PTEN mutation were found in 10% cases and they were all LOH positive. Conclusion: LOH of PTEN gene appears in precancerous lesions and the PTEN mutations are restricted to advanced gastric cancer. It is closely correlated to the infiltration and metastasis of gastric cancer.