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

All colorectal cancer cell lines except RKO displayed active β-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 expre...

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Autores principales: Abdel-Rahman, Wael M., Lotsari-Salomaa, Johanna E., Kaur, Sippy, Niskakoski, Anni, Knuutila, Sakari, Järvinen, Heikki, Mecklin, Jukka-Pekka, Peltomäki, Päivi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800109/
https://www.ncbi.nlm.nih.gov/pubmed/27047543
http://dx.doi.org/10.1155/2016/6089658
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author Abdel-Rahman, Wael M.
Lotsari-Salomaa, Johanna E.
Kaur, Sippy
Niskakoski, Anni
Knuutila, Sakari
Järvinen, Heikki
Mecklin, Jukka-Pekka
Peltomäki, Päivi
author_facet Abdel-Rahman, Wael M.
Lotsari-Salomaa, Johanna E.
Kaur, Sippy
Niskakoski, Anni
Knuutila, Sakari
Järvinen, Heikki
Mecklin, Jukka-Pekka
Peltomäki, Päivi
author_sort Abdel-Rahman, Wael M.
collection PubMed
description All colorectal cancer cell lines except RKO displayed active β-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 β-catenin localizations as a surrogate marker for β-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 with membranous β-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.
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spelling pubmed-48001092016-04-04 The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription Abdel-Rahman, Wael M. Lotsari-Salomaa, Johanna E. Kaur, Sippy Niskakoski, Anni Knuutila, Sakari Järvinen, Heikki Mecklin, Jukka-Pekka Peltomäki, Päivi Gastroenterol Res Pract Research Article All colorectal cancer cell lines except RKO displayed active β-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 β-catenin localizations as a surrogate marker for β-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 with membranous β-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. Hindawi Publishing Corporation 2016 2016-03-07 /pmc/articles/PMC4800109/ /pubmed/27047543 http://dx.doi.org/10.1155/2016/6089658 Text en Copyright © 2016 Wael M. Abdel-Rahman et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Abdel-Rahman, Wael M.
Lotsari-Salomaa, Johanna E.
Kaur, Sippy
Niskakoski, Anni
Knuutila, Sakari
Järvinen, Heikki
Mecklin, Jukka-Pekka
Peltomäki, Päivi
The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription
title The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription
title_full The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription
title_fullStr The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription
title_full_unstemmed The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription
title_short The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription
title_sort role of chromosomal instability and epigenetics in colorectal cancers lacking β-catenin/tcf regulated transcription
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800109/
https://www.ncbi.nlm.nih.gov/pubmed/27047543
http://dx.doi.org/10.1155/2016/6089658
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