错配修复hMLH3基因C2825T和A2173C突变在家族性食管癌中的意义  

Significance of missense mutation of C2825T and A2173C of mismatch repair gene hMLB3 in familial esophageal cancer

作　　者：姜学东[1] 刘宏旭[2] 全利国 关宏宇[4] 孟庆显[1] 

机构地区：[1]武警辽宁总队医院心胸外科,沈阳110034 [2]中国医科大学附属第一医院胸外科,沈阳110001 [3]武警辽宁总队医院门诊部,沈阳110034 [4]辽宁大学化学科学与工程学院,沈阳110036

出　　处：《武警医学》2006年第10期727-730,共4页Medical Journal of the Chinese People's Armed Police Force

基　　金：武警部队科研立项资助项目(WKH2004010)

摘　　要：目的探讨错配修复基因hMLH3在家族性食管癌发病中的突变及其作用。方法应用聚合酶链反应(PCR)、变性高效液相色谱:分析(DHPLC)和直接测序法检测8个有遗传背景的食管癌家族的hMLH3基因突变情况。结果在2个家系中发现了2处错义突变C2825T和A2173C。33％的突变发生于低风险的人群中,而高风险家系中有20％的基因突变。在2个家系中hMLH3的错义突变与食管癌发生有较强的相关性。结论首次发现hMLH3基因C2825T和A2173C错义突变。hMLH3基因作为一新的风险基因,在家族性食管癌的发病中可能通过与其它基因互相叠加、共同起作用。Objective To investigate the role of mismatch repair gene hMLH3 in familial esophageal cancer. Methods The members from eight families with suggestive hereditary esophageal cancer were investigated by PCR, denaturing high performance liquid chromatography and direct performancing. Results All exons of hMLH3 in all samples were successfully examined. Overall, 2 missense mutations were identified in 2 families, hMLH3 missense mutations in family 7 and 8 may be pathogenic, but with reduced penetrance. The mutations were found in 20% of high - risk families and 33% of low - risk families. Conclusions （ 1）The mutations of C2825T and A2173C in hMLH3 have been discovered in human familial esophageal cancer for the first time. （2）As a new risk gene, the mutations of hMLH3 work together with other genes in an additive manner and result in an elevated risk of esophageal tumors in the family.

关 键 词：家族性食管癌 DNA错配修复基因 错义突变 变性高效液相色谱分析 

分 类 号：R734.2[医药卫生—肿瘤]