鼻咽癌染色体9p21～22区域精细缺失图谱的构建

Detailed deletion mapping of chromosome 9p21～22 in nasopharyngeal carcinoma

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,为发现和分离克隆该区域内的鼻咽癌抑瘤基因提供新线索和依据。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。结果 25 例患者中,有17 例存在一个或多个位点的杂合性丢失,占68-0 % 。其中D9S161(35 .0 % ) 、D9S1678(31 .6 % ) 、D9S263(33 .3 % ) 和D9S1853(33 .3 % )4 个紧邻位点的丢失频率相对较高,并发现有6 例患者在这些位点表现为连续性缺失。结论 鼻咽癌染色体9p21 ～22 区域D9S161 ～D9S1853 位点之间(2 .7 cM) 是鼻咽癌患者的一个较小共同缺失区,该区域内的抑瘤基因失活可能是鼻咽癌发生发展过程中的重要事件。

Objective To further refine the extent of deletion on chromosome 9p21～22 in nasopharyneal carcinoma(NPC) and provide evidence for discovering new tumor suppressor genes.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. Results Of the 25 cases, 17(68.0%) showed LOH at one or more loci. Higher frequencies of LOH were found at four loci: D9S161(35.0%), D9S1678(31.6%), D9S263 (33.3%) and D9S1853(33.3%). In 6 cases, contiguous stretch of allelic loss was found.Conclusion The minimal common region of deletion might be defined between D9S161 and D9S1853 (approximately 2.7 cM in length) at 9p21.1, suggesting that inactivation of one or more tumor suppressor genes located in this region may be an important step in NPC.