甲状腺乳头状癌中DNA修复基因hMLH1的甲基化与BRAF突变的关系  

Hypermethylation of DNA repair genes hMLH1 in papillary thyroid cancer and its association with BRAF mutation

作　　者：宝荣[1] 邵华[2] 成建新[3] 王佾[1] 

机构地区：[1]重庆市第九人民医院病理科,400700 [2]中国医科大学附属盛京医院普外三科,沈阳110004 [3]山东省滨州市人民医院病理科,256610

出　　处：《重庆医学》2010年第5期519-521,F0003,共4页Chongqing medicine

摘　　要：目的研究甲状腺乳头状癌(PTC)中DNA修复基因hMLH1的甲基化状况,分析其与PTC的T1799ABRAF基因突变的关系。方法应用甲基化特异性PCR(MSP)对60例PTC和20例癌对侧甲状腺正常组织进行hMLH1的甲基化检测。直接测序法检测上述标本中T1799ABRAF突变。结果60例PTC中,hMLH1甲基化的发生率为23%(14/60),T1799ABRAF突变率为65%(39/60)。在正常甲状腺组织中,没有检测到hMLH1的甲基化或突变。基因的甲基化或突变与临床病理特征没有显著关联。携带T1799ABRAF突变的PTC较携带野生型BRAF基因的PTC更容易发生DNA修复基因的甲基化〔13/39(33%)vs1/21(5%),P=0.022〕。结论PTC中DNA修复基因hMLH1的甲基化较T1799ABRAF突变少见;甲基化与T1799ABRAF突变有关联。Objective To investigate the aberrant hypermethylation of DNA repair genes hMLH1 in papillary thyroid cancer （PTC）,and to analyze its association with T1799A BRAF gene mutation. Methods Promoter methylation status of DNA repair genes hMLH1 in 60 PTCs and 20 normal thyroid tissues was examined using methylation-specific PCR （MSP）. The T1799A BRAF was determined by direct sequencing. Results Among the 60 PTC tumors examined,the hMLH1 gene was hypermethylated in 23% （n= 14） samples. The T1799A BRAF mutation was found in 65% （n=39） samples. Neither methylation of DNA repairs genes nor BRAF mutation was seen in normal thyroid tissues. Methylation of the DNA repairs genes or BRAF mutation was not in relation to clinicopathological features of tumors. Methylation of the DNA repair genes was associated with the T1799A BRAF mutation in PTC[13/39（33%） for the BRAF mutation-positive group vs. 1/21 （50%） for the BRAF mutation-negative group,P= 0. 022]. Conclusion Methylation of the hMLH1 gene is not as common as BRAF mutation in PTC. There seems to be a close relationship between methylation of DNA repair genes and the BRAF mutation.

关 键 词：甲基化 HMLH1基因 BRAF突变 甲状腺癌 

分 类 号：R736.1[医药卫生—肿瘤] R73-37[医药卫生—临床医学]