食管癌组织人乳头瘤病毒感染及其与微卫星杂合性缺失的关系

目的 探讨食管癌组织中14个微卫星位点的杂合性缺失与人乳头瘤病毒(HPV)感染的关系.方法 采用荧光定量PCR法检测112例食管癌标本中HPV-16、18型的感染情况;采用PCR荧光测序仪凝胶电泳检测112例患者匹配的肿瘤和外周血样本中14个微卫星位点的杂合性缺失状况;比较HPV阳性和阴性标本中14个位点的杂合缺失率.结果 染色体3p、9p、13q、17p和17q上的微卫星位点发生了高频的杂合性缺失;发现在2个位点处--D6S497和D13S260,HPV阳性的标本较阴性的拥有更高的杂合性缺失率.结论 缺失涉及众多位点反映出食管癌中基因组存在广泛的不稳定现象;HPV阳性标本在D13S260和D6S497两个位点处拥有更高的杂合缺失率提示食管癌中HPV的作用靶点可能是位于这两个位点处的某些候选基因;另外,四川省是食管癌高发区,该结果也说明HPV是当地食管癌的一重要高危因素.

Study on human papillomavirus infection and loss of heterozygosity of microsatellite in esophageal cancer

OBJECTIVE: To investigate the relationship between the loss of heterozygosity(LOH) at 14 microsatellites in esophageal cancer and human papillomavirus (HPV) infection. METHODS: HPV-16,18 DNA was examined in 112 tumor specimens using fluorescence quantitative PCR. 112 tumor specimens and their matched blood DNAs were analyzed for LOH at 14 microsatellites by PCR and fluorescence-based DNA sequencing technology. The frequencies of LOH at 14 microsatellites were compared between HPV positive and negative specimens. RESULTS: High frequency of LOH was observed among chromosome arms 3p, 9p, 13q, 17p and 17q. The frequency of LOH was significantly higher at loci D13S260 and D6S497 in HPV positive specimens, comparing with HPV negative ones. CONCLUSION: The findings regarding loci with allele loss indicated that widespread chromosome instability might have existed in esophageal cancer. HPV positive specimens with higher frequency of LOH than negative ones at locus D13S260 and D6S497 suggesting that the target of HPV in esophageal cancer might serve as candidate genes at these two loci. In addition,this result also indicated that HPV might be a high-risk factor for esophageal cancer in Sichuan area with a high incidence of this cancer.