口腔鳞癌中染色体9p、9q的杂合性丢失及p16表达的研究

检测９号染色体及ｐ１６基因在口腔鳞癌发生发展中的作用。方法：应用聚合酶链反应技术，检测经显微切割的口腔鳞癌组织中两个ＤＮＡ微卫星多态标记ＤｑＳ３１９（９ｐ２１）和ＤｑＳ２９９（９ｑ２２～３１），分析染色体９ｐ、９ｑ的杂合性丢失情况。同时应用免疫组织化学方法观察其ｐ１６蛋白表达状况。结果：２９．４％出现ＤｑＳ３１９标记的ＬＯＨ，ＤｑＳ２９９标记发现较高频率ＬＯＨ（４３．８％）。ｐ１６蛋白免疫组化染色阳性率为８６．４％。其中３例未表达ｐ１６的标本中，有２例发现ＤｑＳ３１９的ＬＯＨ。结论：口腔鳞癌在染色体９ｐ２１区域频繁丢失可能与ｐ１６失活有关，而染色体９ｑ２２～３１区域在口腔鳞癌的较高频率丢失推测此区可能存在与肿瘤发生密切相关的抑癌基因。

Loss of Heterozygosity of Chromosome 9p, 9q and Expression of p16in Oral Squamous Cell Carcinoma

Inactivation of tumor suppressor gene due to allelic loss is thought to be an important mech-anism of gene alteration in oral cancer. It has been suggested that loss of both arms of chromosome 9 isone of the most frequent abnormalities in human head and neck cancers and that one or more putative tu-mor suppressor gene(s) which may contribute to the initiation and/or progression of these tumors mightbe located on chromosome 9. Oral squamous cell carcinoma is one type of the head and neck cancers. Toinvestigate the potential loss of tumor suppressor gene loci on chromosome 9p, 9q in oral squamous cellcarcinogenesis, we analyzed 22 paired samples of normal tissues and squamous cell carcinoma from thesame patients. Tissue microdissection under direct microscopic visualization procured pure population ofsquamous cells. LOH was detected by examining microsatellite polymorphic sequences in loci DqS319(9p21) and DqS299 (9q22 -31) by using PCR. In 5 of 17 (29.4% ), LOH was found at 9p21(DqS319) , and p16 protein was detectable in 86. 4% of the samples. p16/CDKN2 gene was involved inthe chromosome 9p deletion in oral cancer. A high frequency of allelic loss was found on chromosome 9qwhere 7 of 16 (43. 8% ) tumors had LOH at 9q22-31 ( DqS299) . This suggests that there is presence ofa novel tumor suppressor gene at chromosome 9q22 - 31 and that this gene is probably related to the oralsquamous cell carcinogenesis.