Show simple item record Udvardyné Galamb, Orsolya Kalmár, Alexandra Péterfia, Bálint Csabai, István Bodor, András Ribli, Dezső Krenács, Tibor Patai, Árpád V Wichmann, Barnabás Barták, Barbara Kinga Tóth, Kinga Valcz, Gábor Tulassay, Zsolt Molnár, Béla 2018-06-12T11:30:21Z 2018-06-12T11:30:21Z 2016
dc.identifier 84976532755
dc.identifier.citation pagination=588-602; journalVolume=11; journalIssueNumber=8; journalTitle=EPIGENETICS;
dc.identifier.uri doi:10.1080/15592294.2016.1190894
dc.description.abstract The WNT signaling pathway has an essential role in colorectal carcinogenesis and progression, which involves a cascade of genetic and epigenetic changes. We aimed to analyze DNA methylation affecting the WNT pathway genes in colorectal carcinogenesis in promoter and gene body regions using whole methylome analysis in 9 colorectal cancer, 15 adenoma, and 6 normal tumor adjacent tissue (NAT) samples by methyl capture sequencing. Functional methylation was confirmed on 5-aza-2′-deoxycytidine-treated colorectal cancer cell line datasets. In parallel with the DNA methylation analysis, mutations of WNT pathway genes (APC, β-catenin/CTNNB1) were analyzed by 454 sequencing on GS Junior platform. Most differentially methylated CpG sites were localized in gene body regions (95% of WNT pathway genes). In the promoter regions, 33 of the 160 analyzed WNT pathway genes were differentially methylated in colorectal cancer vs. normal, including hypermethylated AXIN2, CHP1, PRICKLE1, SFRP1, SFRP2, SOX17, and hypomethylated CACYBP, CTNNB1, MYC; 44 genes in adenoma vs. NAT; and 41 genes in colorectal cancer vs. adenoma comparisons. Hypermethylation of AXIN2, DKK1, VANGL1, and WNT5A gene promoters was higher, while those of SOX17, PRICKLE1, DAAM2, and MYC was lower in colon carcinoma compared to adenoma. Inverse correlation between expression and methylation was confirmed in 23 genes, including APC, CHP1, PRICKLE1, PSEN1, and SFRP1. Differential methylation affected both canonical and noncanonical WNT pathway genes in colorectal normal-adenoma-carcinoma sequence. Aberrant DNA methylation appears already in adenomas as an early event of colorectal carcinogenesis. © 2016 Taylor & Francis Group, LLC
dc.relation.ispartof urn:issn:1559-2294
dc.title Aberrant DNA methylation of WNT pathway genes in the development and progression of CIMP-negative colorectal cancer
dc.type Journal Article 2018-06-06T12:55:33Z
dc.language.rfc3066 en
dc.identifier.mtmt 3097618
dc.identifier.wos 000382380500004
dc.identifier.pubmed 27245242
dc.contributor.department SE/AOK/I/I. Sz. Patológiai és Kísérleti Rákkutató Intézet
dc.contributor.department SE/AOK/I/IISZPI/MTA-SE Molekuláris Onkológia Kutatócsoport
dc.contributor.institution Semmelweis Egyetem

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