The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking beta-Catenin/TCF Regulated Transcription

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Abdel-Rahman , W M , Lotsari-Salomaa , J E , Kaur , S , Niskakoski (o.s. Tieva) , A , Knuutila , S , Järvinen , H , Mecklin , J-P & Peltomaki , P 2016 , ' The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking beta-Catenin/TCF Regulated Transcription ' , Gastroenterology Research and Practice . https://doi.org/10.1155/2016/6089658

Title: The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking beta-Catenin/TCF Regulated Transcription
Author: Abdel-Rahman, Wael M.; Lotsari-Salomaa, Johanna E.; Kaur, Sippy; Niskakoski (o.s. Tieva), Anni; Knuutila, Sakari; Järvinen, Heikki; Mecklin, Jukka-Pekka; Peltomaki, Paivi
Contributor: University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Heikki Järvinen / Principal Investigator
University of Helsinki, Medicum
Date: 2016
Language: eng
Number of pages: 11
Belongs to series: Gastroenterology Research and Practice
ISSN: 1687-6121
URI: http://hdl.handle.net/10138/161405
Abstract: All colorectal cancer cell lines except RKO displayed active beta-catenin/TCF regulated transcription. This feature of RKO was noted in familial colon cancers; hence our aim was to dissect its carcinogenic mechanism. MFISH and CGH revealed distinct instability of chromosome structure in RKO. Gene expression microarray of RKO versus 7 colon cancer lines (with active Wnt signaling) and 3 normal specimens revealed 611 differentially expressed genes. The majority of the tested gene loci were susceptible to LOH in primary tumors with various beta-catenin localizations as a surrogate marker for beta-catenin activation. The immunohistochemistry of selected genes (IFI16, RGS4, MCTP1, DGKI, OBCAM/OPCML, and GLIPR1) confirmed that they were differentially expressed in clinical specimens. Since epigenetic mechanisms can contribute to expression changes, selected target genes were evaluated for promoter methylation in patient specimens from sporadic and hereditary colorectal cancers. CMTM3, DGKI, and OPCML were frequently hypermethylated in both groups, whereas KLK10, EPCAM, and DLC1 displayed subgroup specificity. The overall fraction of hypermethylated genes was higher in tumors withmembranous beta-catenin. We identified novel genes in colorectal carcinogenesis that might be useful in personalized tumor profiling. Tumors with inactive Wnt signaling are a heterogeneous group displaying interaction of chromosomal instability, Wnt signaling, and epigenetics.
Subject: MICROSATELLITE INSTABILITY
LYNCH-SYNDROME
TUMOR-SUPPRESSOR
COLON-CANCER
CELL-LINES
GENE-EXPRESSION
MISMATCH REPAIR
BRAF MUTATION
STEM-CELLS
CARCINOMAS
3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
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