Genetic and epigenetic alterations of WWOX in the development of gastric cardia adenocarcinoma
Genetic and epigenetic alterations of WWOX in the development of gastric cardia adenocarcinoma
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DOI：
10.1002/em.21748
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发表时间：
2013-03-01
影响因子：
2.8
通讯作者：
Yang, Zhibin
中科院分区：
文献类型：
--
作者：
Guo, Wei;Dong, Zhiming;Yang, Zhibin
WWOX是一种肿瘤抑制基因，定位于常见的脆性位点FRA16D，在许多不同的癌症中参与了癌症的发生和发展。在几种癌症中，WWOX表达减少与更具侵袭性的表型和不良的患者预后相关。本研究是为了更准确地阐明WWOX基因的遗传和表观遗传学改变在中国北部人群的贲门腺癌发生中所起的作用。分别采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)、聚合酶链式反应-简单序列长度多态性(PCR-SSLP)和甲基化特异性聚合酶链式反应(MSP)方法分析rs3764340、rs2548861和rs1079635基因座的多态、杂合性缺失(LOH)水平和WWOX的甲基化状态。免疫组织化学和逆转录-聚合酶链式反应(RT-PCR)定量检测GCA组织中WWOX蛋白和mRNA的表达。上消化道癌家族史(UGIC)显著增加发生GCA的风险。Rs3764340的CG+GG和rs2548861的GT或TT等位基因显著增加发生GCA的风险。45.6%的肿瘤存在WWOX基因的杂合性缺失。GCA组织中WWOX基因启动子和外显子1甲基化频率明显高于相应的正常组织，且与UGIC家族史有关。在GCA肿瘤组织中，WWOX的蛋白和mRNA表达降低，并与该基因的杂合性缺失和甲基化有关。提示WWOX可能在GCA中起重要作用，尤其是在有UGIC家族史的个体中。环境。摩尔。《诱变剂》，2013年。(C)2012年威利期刊公司。
WWOX is a tumor suppressor gene that maps to the common fragile site FRA16D and is involved in carcinogenesis and cancer progression in many different carcinomas. Reduced WWOX expression is associated with more aggressive phenotypes and poor patient outcomes in several cancers. The present study was conducted in order to elucidate more precisely the genetic and epigenetic alterations of WWOX that play a role in gastric cardia adenocarcinoma (GCA) carcinogenesis in a population from Northern China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), PCR-simple sequence length polymorphism (PCR-SSLP), and methylation specific PCR (MSP) methods were used to characterize polymorphisms in the rs3764340, rs2548861, and rs1079635 loci, the level of loss of heterozygosity (LOH), and methylation status of WWOX, respectively. Protein and mRNA expression of WWOX in GCA tissues was quantified by immunohistochemistry and reverse transcription-PCR (RT-PCR). Family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing GCA. The CG+GG genotype of rs3764340 and GT or TT genotype of rs2548861 significantly elevated the risk of developing GCA. LOH at the WWOX locus was observed in 45.6% tumors. The promoter and exon 1 methylation frequency of WWOX in GCA tissues was significantly higher than in corresponding normal tissues and was associated with UGIC family history. Protein and mRNA expression of WWOX was reduced in GCA tumor tissues and was associated with LOH and methylation of the gene. These results indicate that WWOX may play an important role in GCA especially in individuals with UGIC family history. Environ. Mol. Mutagen., 2013. (c) 2012 Wiley Periodicals, Inc.