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dc.contributor.author Kalmár, Alexandra
dc.contributor.author Péterfia, Bálint
dc.contributor.author Hollósi, Péter
dc.contributor.author Udvardyné Galamb, Orsolya
dc.contributor.author Spisák, Sándor
dc.contributor.author Wichmann, Barnabás
dc.contributor.author Bodor, András
dc.contributor.author Tóth, Kinga
dc.contributor.author Patai, Árpád V
dc.contributor.author Valcz, Gábor
dc.contributor.author Nagy, Zsófia
dc.contributor.author Vivien Kubák
dc.contributor.author Tulassay, Zsolt
dc.contributor.author Kovalszky, Ilona
dc.contributor.author Molnár, Béla
dc.date.accessioned 2016-06-30T08:33:02Z
dc.date.available 2016-06-30T08:33:02Z
dc.date.issued 2015
dc.identifier.citation pagination=736, pages 14; journalVolume=15; journalTitle=BMC CANCER;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/2816
dc.identifier.uri doi:10.1186/s12885-015-1687-x
dc.description.abstract BACKGROUND: Colorectal cancer (CRC) development is accompanied by changes in expression for several genes; but the details of the underlying regulatory procesess remain unknown. Our aims were to assess the role of epigenetic processes in tumour formation and to identify characteristic DNA methylation and miRNA alterations in the colorectal adenoma-carcinoma sequence. METHODS: Whole genome expression profiling was performed on colonic biopsy samples (49 healthy normal, 49 colorectal adenoma (AD), 49 CRC); on laser capture microdissected (LCM) epithelial and stromal cells from 6 CRC-normal adjacent tissue (NAT) samples pairs, and on demethylated human CRC cell lines using HGU133 Plus 2.0 microarrays (Affymetrix). Methylation status of genes with gradually altering expression along the AD-CRC sequence was further analysed on 10-10 macrodissected and 5-5 LCM samples from healthy colon, from adenoma and from CRC biopsy samples using bisulfite-sequencing PCR (BS-PCR) followed by pyrosequencing. In silico miRNA prediction for the selected genes was performed with miRWALK algorithm, miRNA expression was analysed on 3 CRC-NAT sample pairs and 3 adenoma tissue samples using the Human Panel I + II (Exiqon). SFRP1 immunohistochemistry experiments were performed. RESULTS: A set of transcripts (18 genes including MAL, SFRP1, SULT1A1, PRIMA1, PTGDR) showed decreasing expression (p < 0.01) in the biopsy samples along the adenoma-carcinoma sequence. Three of those (COL1A2, SFRP2, SOCS3) showed hypermethylation and THBS2 showed hypomethylation both in AD and in CRC samples compared to NAT, while BCL2, PRIMA1 and PTGDR showed hypermethylation only in the CRC group. miR-21 was found to be significantly (p < 0.01) upregulated in adenoma and tumour samples compared to the healthy colonic tissue controls and could explain the altered expression of genes for which DNA methylation changes do not appear to play role (e.g. BCL2, MAL, PTGS2). Demethylation treatment could upregulate gene expression of genes that were found to be hypermethylated in human CRC tissue samples. Decreasing protein levels of SFRP1 was also observed along the adenoma-carcinoma sequence. CONCLUSION: Hypermethylation of the selected markers (MAL, PRIMA1, PTGDR and SFRP1) can result in reduced gene expression and may contribute to the formation of colorectal cancer.
dc.relation.ispartof urn:issn:1471-2407
dc.title DNA hypermethylation and decreased mRNA expression of MAL, PRIMA1, PTGDR and SFRP1 in colorectal adenoma and cancer
dc.type Journal Article
dc.date.updated 2015-11-26T15:11:04Z
dc.language.rfc3066 en
dc.identifier.mtmt 2958539
dc.contributor.department SE/AOK/K/IISZBK/MTA-SE Molekuláris Medicina Kutatócsoport (2006-ig: MTA-SE Gastroenterológiai és Endocrinológiai Kutatócsoport)
dc.contributor.department SE/AOK/K/II. Sz. Belgyógyászati Klinika
dc.contributor.department SE/AOK/I/I. Sz. Patológiai és Kísérleti Rákkutató Intézet
dc.contributor.institution Semmelweis Egyetem


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