Aberrant methylation of DAPK in long-standing ulcerative colitis and ulcerative colitis-associated carcinoma

Pathology, Research and Practice
Doerthe KuesterRegine Schneider-Stock

Abstract

Death-associated protein kinase (DAPK) has pro-apoptotic functions and participates in various apoptotic systems. DAPK acts as a tumor suppressor, and its inactivation by promoter hypermethylation has been frequently observed in various human cancers. As alterations of pro-apoptotic genes might cause instability in the balance of cell-turnover during chronic inflammatory processes, epigenetic silencing of DAPK might be involved in the carcinogenesis of ulcerative colitis-associated carcinoma (UCC). To evaluate the role of DAPK in the inflammation-driven carcinogenesis of ulcerative colitis (UC), we analyzed promoter hypermethylation and protein expression of DAPK using methylation-specific PCR and immunohistochemistry in 43 UCCs and paired UC-background mucosa, as well as in UC-background mucosa of 50 patients without UCC. The frequency of methylation of DAPK in UCCs was low (27.6%) compared to overall non-neoplastic UC-background mucosa (48.3%; p=0.02) and sporadic colorectal carcinoma (57.4%, p=0.019). The difference in the methylation frequency in UC-background mucosa in patients without UCC (54.2%), compared to those with UCC (40.0%), was not significant (p=0.141). Promoter methylation correlated significantly with decrease...Continue Reading

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Citations

Dec 7, 2013·Apoptosis : an International Journal on Programmed Cell Death·Yide HuangYao Lin
Nov 13, 2013·Apoptosis : an International Journal on Programmed Cell Death·Natalya Benderska, Regine Schneider-Stock
Nov 5, 2013·Apoptosis : an International Journal on Programmed Cell Death·Ming-Zong Lai, Ruey-Hwa Chen
Apr 27, 2012·Gastroenterology Research and Practice·Angharad R MorganLynnette R Ferguson
Sep 22, 2011·Inflammatory Bowel Diseases·Amrita KabiChristine McDonald
Oct 15, 2011·American Journal of Respiratory Cell and Molecular Biology·Sigal NakavRonen Alon
Feb 27, 2013·The American Journal of Pathology·Saritha ChakilamRegine Schneider-Stock
Feb 15, 2017·Pancreas·Yasuhiro KinugawaHiroyoshi Ota
Jul 23, 2019·Journal of Neurogastroenterology and Motility·Brian G Jorgensen, Seungil Ro
Aug 19, 2014·World Journal of Gastroenterology : WJG·Luciana Rigoli, Rosario Alberto Caruso
Jun 18, 2017·Epigenomics·Ruth A EmmettRamesh P Arasaradnam
Mar 27, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Shu-Nan CuiYou Shang
Nov 1, 2017·World Journal of Gastroenterology : WJG·Karen Dubois-CamachoMarcela A Hermoso
Apr 10, 2020·United European Gastroenterology Journal·Marie MullerLaurent Peyrin-Biroulet
Oct 6, 2018·International Journal of Molecular Sciences·Mohamed ElbadawyKazuaki Sasaki
Jun 27, 2018·Inflammatory Bowel Diseases·Meng XueLiangjing Wang

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