APC、MYH及AXIN2基因突变检测在家族性腺瘤性息肉病胚系突变筛查中的应用  

Detection of APC, MYH and AXIN2 gene mutations for screening germline mutations predisposing to familial adenomatous polyposis

作　　者：杨军[1] 刘为青[2] 李文亮[1] 陈诚[1] 珠珠[1] 王志强[1] 董坚[2] 

机构地区：[1]昆明医科大学第一附属医院肿瘤科,云南省昆明市650032 [2]昆明医科大学第一附属医院肿瘤内科,云南省昆明市650032

出　　处：《世界华人消化杂志》2015年第4期556-562,共7页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81160245;云南省科学技术联合专项基金资助项目;No.2011FB160~~

摘　　要：目的:通过对本实验室中已收集的云南省遗传性大肠癌标本库中的家族性腺瘤性息肉病(familial adenomatous polyposis,F A P)家系标本进行F A P常见致突变基因APC(adenomatous polyposis coli)基因的筛查,对APC基因筛查为阴性的标本则进一步行MYH(Mut Y Homologue)基因及轴抑制蛋白(axis inhibition protein 2,AXIN2)基因检测,探讨FAP家系患者的致病基因及其突变位点.方法:利用已建立的云南省遗传性大肠癌标本库中家系标本进行DNA的提取,PCR特异性扩增APC基因所有外显子和启动子区域,分析APC基因及其启动子是否存在点突变;对于APC基因筛查未见突变者,继续行MYH和AXIN2基因全外显子检测.结果:在所选的5个FAP家系成员的DNA中,1个家系中的1例患者检测出A P C基因新的突变(100025_100028het_dup AGAA),其余4个家系患者未检测到APC基因致病性突变;而对于APC基因突变阴性者进行的MYH基因突变筛查中,其中一个家系中的1例患者发现了新的突变(11198_11200het_del TGT);而在AXIN2基因检测中,检出4个同义突变,其中,同义突变c.2062C>T(p.L688L)为已报道的致病性突变.结论:相较于国内外同类研究报道,云南省FAP家系成员APC基因突变检出率较低,针对MYH及AXIN2基因检测同时也应作为FAP致病基因筛查的靶点.AIM： To investigate the significance of detection of APC, MYH and AXIN2 gene mutations in familial adenomatous polyposis（FAP） patients for screening germline mutations predisposing to FAP. METHODS： Potential APC gene mutations were detected in 5 FAP patients from Yunnan Province, China, by exon-specific DNA sequencing. For samples without alreadyknown APC gene mutations predisposing to FAP, whole-gene sequencing of the MYH and AXIN2 genes was performed. RESULTS： One novel heterozygous duplication（1119811200hetdel TGT） of the APC gene was observed. One novel heterozygous deletion（1119811200hetdel TGT） was detected in the MYH gene. Four synonymous mutations were found in the AXIN2 gene, of which c.2062C〉T（p.L688L） was reported to be a pathogenic mutation.CONCLUSION： Compared with similar research reports, the positive rate of germline mutation of the APC gene is relatively low in Yunnan Province. To get the full picture of germline mutations predisposing to FAP, MYH and AXIN2 genes should also be tested for FAP pathogenic gene screening.

关 键 词：家族性腺瘤性息肉病 APC基因 MYH基因 AXIN2基因 

分 类 号：R735[医药卫生—肿瘤]