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精细定位和克隆9p21-22区域内鼻咽癌候选抑瘤基因

Refined localization and cloning of a novel putative tumor suppressor gene associated with nasopharyngeal carcinoma on chromosome 9p21-22

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【作者】 阳剑波宾亮华李忠花张小慧钱骏张必成周鸣谢奕邓龙文李桂源

【Author】 YANG Jian-bo, BIN liang-hua, LI zhong-hua, et al. (Cancer Research Institute, Hunan Medical University, Changsha 410078, P. R. China)

【机构】 湖南医科大学肿瘤研究所!湖南长沙 410078湖南医科大学肿瘤研究?

【摘要】 目的:进一步精细限定鼻咽癌9p21-22区域等位基因杂合性丢失的频率和范围,筛选和克隆其共同缺失区内鼻咽癌相关的候选抑瘤基因。方法:应用11个定位于 9p21-22区域的高密度微卫星位点,检测 25例低分化鼻咽癌患者的杂合性丢失,确定其共同缺失区;用RT-PCR和Northern筛出在鼻咽癌细胞株HNE1和鼻咽癌活检组织中表达下调的、定位于共同缺失区内的 3’末端ESTs(Express Sequence Tags);采用 RACE技术和生物信息学资源克隆出候选EST的全长cDNA。结果: 25例患者中有17例(68%)存在一个或多个位点的杂合性丢失,其中D9s161(35.0%,7/20),D9S1678(31.5%,6/19),D9S263(3.3%,6/18)和D9S1853(33.3%,7/21)四个紧邻位点的丢失频率相对较高,并发现六位患者在该四个位点表现为连续性缺失;筛选D9S161-D9S1853区域内25个代表新基因的3’末端ESTs序列,发现一个EST(dbEST:208825)在鼻咽癌细胞株HNE1及73%(11/15)的活检组织中表达降低, Multiple Tissue Nort hem(MTN

【Abstract】 Objectives: To further refine the extent of deletion on chromosome gp21-22 in nasopharyngeal carcinoma (NPC) and clone a new putative tumor suppressor gene associated with NPC. Methods: Loss of heterozygosity (LOH) on chromosome 9p21 -22 was analyzed in 25 paired blood and tumor samples by using 11 high-density microsatellite polymorphic markers; the expression of 3’ end express sequence tags (ESTs) localized with in common deletion region was investigated tri NPC cell line HNE1, primary culture nasopharyngeal epithelial cells and BPC biopsies by using differential RT-PCR and Northern hybridization. Rapid amplification of cDNA ends (RACE) and bioinformatic data were used to clone putative EST, full-length cDNA. Results: Seventeen of 25 cases (68%) showed LOH at one or more loci. Higher frequencies of LOH were found at four loci: D9S161 (35. 0% ), D9S1678 (31.5% ), D9S263 (33. 3% ) and D9S1853 (33.3% ), where 6 cases had a contiguous stretch of allelic loss; 25 ESTs localized within D9S161 - D9S1853 were investigated and one EST (dbESI: 208825) was downexpressed in NPC cell line HNE1 and in 73% (11 / 15) NPC biopsies. Multiple tissue blot revealed that this putative EST hybridized to two different size transcripts (approximately 2.4 kb) and 3.5 kb) in fetal heart and brain tissues. A near full-length cDNA of 2.4 kb transcript of this EST was cloned(named NAG-6 gene) and there is no significant homology with any known genes. Conclusions: The minimal common region of deletion might he defined between D9S161 and D9S1853 (estimated about 2.7 cM in extent) at 9p21.1, the new gene NAG-6 located in this region may be a putative tumor suppressor gene associated with NPC.

【基金】 国家863项目!(102-10-01-05);973重大项目(“疾病基因组学”理论和技术体系的建立鼻咽癌子项目)资助
  • 【文献出处】 癌症 ,CHINESE JOURNAL OF CANCER , 编辑部邮箱 ,2000年01期
  • 【分类号】R739.63
  • 【被引频次】55
  • 【下载频次】101
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