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散发性结直肠癌中病毒DNA序列的检测及其与CpG岛甲基化和甲基化表型的关系。

Detection of viral DNA sequences in sporadic colorectal cancers in relation to CpG island methylation and methylator phenotype.

作者信息

Karpinski Pawel, Myszka Aleksander, Ramsey David, Kielan Wojciech, Sasiadek Maria Malgorzata

机构信息

Department of Genetics, Wroclaw Medical University, ul. Marcinkowskiego 1, 50-368, Wroclaw, Poland.

出版信息

Tumour Biol. 2011 Aug;32(4):653-9. doi: 10.1007/s13277-011-0165-6. Epub 2011 Apr 6.

Abstract

There is evidence that insertion of viral DNA into a mammalian genome can lead to alterations of methylation patterns. The aim of the present study was to examine the presence of DNA sequences of five human DNA viruses (assessed by PCR): JC polyoma virus (JCV), human adenovirus (AdV), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV/HHV8) and human papillomavirus (HPV) in a cohort of 186 sporadic colorectal cancers (CRCs) and related these data with the methylation status of six CpG island methylator phenotype (CIMP)-specific genes (MLH1, CACNA1G, NEUROG1, IGF2, SOCS1, RUNX3) and seven cancer-related genes markers (p16, MINT1, MINT2, MINT31, EN1, SCTR and INHBB) assessed by methylation-specific PCR in 186 and 134 CRC cases, respectively. The AdV, KSHV and HPV were detected in four (2%), two (1%) and zero CRC cases, respectively, and thus were excluded from further analyses. Although 19% and 9% of the CRCs were positive for EBV and JCV, respectively, no associations between virus presence and CpG island methylation were found after correction for multiple testing. Our results demonstrate that the presence of DNA sequences of JCV and EBV in CRC is unrelated to the methylation of the 13 cancer-related CpG islands and CIMP.

摘要

有证据表明,病毒DNA插入哺乳动物基因组可导致甲基化模式改变。本研究的目的是检测186例散发性结直肠癌(CRC)患者中5种人类DNA病毒(通过PCR评估)的DNA序列:JC多瘤病毒(JCV)、人腺病毒(AdV)、爱泼斯坦-巴尔病毒(EBV)、卡波西肉瘤相关疱疹病毒(KSHV/HHV8)和人乳头瘤病毒(HPV),并将这些数据与186例和134例CRC病例中通过甲基化特异性PCR评估的6个CpG岛甲基化表型(CIMP)特异性基因(MLH1、CACNA1G、NEUROG1、IGF2、SOCS1、RUNX3)和7个癌症相关基因标志物(p16、MINT1、MINT2、MINT31、EN1、SCTR和INHBB)的甲基化状态相关联。分别在4例(2%)、2例(1%)和0例CRC病例中检测到AdV、KSHV和HPV,因此将其排除在进一步分析之外。尽管分别有19%和9%的CRC患者EBV和JCV呈阳性,但在多重检验校正后,未发现病毒存在与CpG岛甲基化之间存在关联。我们的结果表明,CRC中JCV和EBV的DNA序列存在与13个癌症相关CpG岛和CIMP的甲基化无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/997c/3131518/c604668a850e/13277_2011_165_Fig1_HTML.jpg

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