Methylation profile analysis of DNA repair genes in hepatocellular carcinoma with MS-MLPA.

Ozge Ozer, Banu Bilezikci, Sema Aktas, Feride I Sahin
{"title":"Methylation profile analysis of DNA repair genes in hepatocellular carcinoma with MS-MLPA.","authors":"Ozge Ozer,&nbsp;Banu Bilezikci,&nbsp;Sema Aktas,&nbsp;Feride I Sahin","doi":"10.1097/PDM.0b013e31828ed856","DOIUrl":null,"url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the rare tumors with well-defined risk factors. The multifactorial etiology of HCC can be explained by its complex molecular pathogenesis. In the current study, the methylation status of 7 genes involved in DNA repair mechanisms, namely MLH1, PMS2, MSH6, MSH2, MGMT, MSH3, and MLH3, was investigated in tumor samples from HCC patients, using the methylation-specific-multiplex ligated probe amplification method and the results were correlated with available clinical findings. The most common etiological factor in these cases was the presence of hepatitis B alone (47.2%). Among the 56 cases that were studied, promoter methylation was detected in at least one of the genes in 27 (48.2%) cases, only in 1 gene in 13 (23.2%) cases, and in >1 gene in 14 (25%) cases. Of the 7 genes investigated, methylation was most frequently observed in MSH3, in 14 (25%) cases. Methylation of at least 1 gene was significantly more frequent in patients with single tumors than multifocal tumors. There were significant differences regarding hepatitis B status, Child Class, tumor number, grade, and TNM stage in cases where PMS2 methylation was detected. Our results suggest that methylation of genes involved in mismatch repair may be responsible in the pathogenesis of HCC, and evaluating changes in multiple genes in these pathways simultaneously would be more informative. Despite being a robust and relatively inexpensive method, the methylation-specific-multiplex ligated probe amplification assay could be more extensively applied with improvements in the currently intricate data analysis component. </p>","PeriodicalId":11235,"journal":{"name":"Diagnostic Molecular Pathology","volume":"22 4","pages":"222-7"},"PeriodicalIF":0.0000,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/PDM.0b013e31828ed856","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diagnostic Molecular Pathology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1097/PDM.0b013e31828ed856","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3

Abstract

Hepatocellular carcinoma (HCC) is one of the rare tumors with well-defined risk factors. The multifactorial etiology of HCC can be explained by its complex molecular pathogenesis. In the current study, the methylation status of 7 genes involved in DNA repair mechanisms, namely MLH1, PMS2, MSH6, MSH2, MGMT, MSH3, and MLH3, was investigated in tumor samples from HCC patients, using the methylation-specific-multiplex ligated probe amplification method and the results were correlated with available clinical findings. The most common etiological factor in these cases was the presence of hepatitis B alone (47.2%). Among the 56 cases that were studied, promoter methylation was detected in at least one of the genes in 27 (48.2%) cases, only in 1 gene in 13 (23.2%) cases, and in >1 gene in 14 (25%) cases. Of the 7 genes investigated, methylation was most frequently observed in MSH3, in 14 (25%) cases. Methylation of at least 1 gene was significantly more frequent in patients with single tumors than multifocal tumors. There were significant differences regarding hepatitis B status, Child Class, tumor number, grade, and TNM stage in cases where PMS2 methylation was detected. Our results suggest that methylation of genes involved in mismatch repair may be responsible in the pathogenesis of HCC, and evaluating changes in multiple genes in these pathways simultaneously would be more informative. Despite being a robust and relatively inexpensive method, the methylation-specific-multiplex ligated probe amplification assay could be more extensively applied with improvements in the currently intricate data analysis component.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
肝癌DNA修复基因甲基化谱的MS-MLPA分析。
肝细胞癌是一种危险因素明确的罕见肿瘤。HCC的多因素病因可以通过其复杂的分子发病机制来解释。本研究采用甲基化特异性多重连接探针扩增方法,对肝癌患者肿瘤样本中参与DNA修复机制的7个基因MLH1、PMS2、MSH6、MSH2、MGMT、MSH3、MLH3的甲基化状态进行了研究,结果与已有临床结果相关。这些病例中最常见的病因是单纯存在乙型肝炎(47.2%)。在所研究的56例病例中,27例(48.2%)病例中至少有一个基因存在启动子甲基化,13例(23.2%)病例中只有一个基因存在启动子甲基化,14例(25%)病例中>1基因存在启动子甲基化。在研究的7个基因中,甲基化在MSH3中最常见,在14例(25%)病例中观察到。至少1个基因的甲基化在单个肿瘤患者中比多灶性肿瘤患者明显更频繁。在检测到PMS2甲基化的病例中,在乙型肝炎状态、儿童类别、肿瘤数量、分级和TNM分期方面存在显著差异。我们的研究结果表明,参与错配修复的基因甲基化可能与HCC的发病机制有关,同时评估这些途径中多个基因的变化将提供更多信息。尽管是一种强大且相对便宜的方法,甲基化特异性多重连接探针扩增试验可以更广泛地应用于目前复杂的数据分析组件的改进。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Diagnostic Molecular Pathology focuses on providing clinical and academic pathologists with coverage of the latest molecular technologies, timely reviews of established techniques, and papers on the applications of these methods to all aspects of surgical pathology and laboratory medicine. It publishes original, peer-reviewed contributions on molecular probes for diagnosis, such as tumor suppressor genes, oncogenes, the polymerase chain reaction (PCR), and in situ hybridization. Articles demonstrate how these highly sensitive techniques can be applied for more accurate diagnosis.
期刊最新文献
Index Molecular Testing for Respiratory Viruses Molecular Testing in Emerging Infectious Diseases Frequent PIK3CA mutations in radial scars. Pyrosequencing for EGFR mutation detection: diagnostic accuracy and clinical implications.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1