Web of Science: 18 citations, Scopus: 19 citations, Google Scholar: citations,
Methylation of MGMT and ADAMTS14 in normal colon mucosa : biomarkers of a field defect for cancerization preferentially targeting elder African-Americans
Alonso, Sergio (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Dai, Yuichi (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Yamashita, Kentaro (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Horiuchi, Shina (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Dai, Tomoko (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Matsunaga, Akihiro (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Sánchez Muñoz, Rosa (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Bilbao Sieyro, Cristina (Instituto Canario de Investigación del Cáncer)
Díaz Chico, Juan Carlos (Instituto Canario de Investigación del Cáncer)
Chernov, Andrei V. (Sanford Burnham Prebys Medical Discovery Institute (Califòrnia))
Strongin, Alex Y. (Sanford Burnham Prebys Medical Discovery Institute (Califòrnia))
Perucho, Manuel (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)

Date: 2015
Abstract: Somatic hypermethylation of the O6-methylguanine-DNA methyltransferase gene (MGMT) was previously associated with G > A transition mutations in KRAS and TP53 in colorectal cancer (CRC). We tested the association of MGMT methylation with G > A mutations in KRAS and TP53 in 261 CRCs. Sixteen cases, with and without MGMT hypermethylation, were further analyzed by exome sequencing. No significant association of MGMT methylation with G > A mutations in KRAS, TP53 or in the whole exome was found (p > 0. 5 in all comparisons). The result was validated by in silico comparison with 302 CRCs from The Cancer Genome Atlas (TCGA) consortium dataset. Transcriptional silencing associated with hypermethylation and stratified into monoallelic and biallelic. We also found a significant clustering (p = 0. 001) of aberrant hypermethylation of MGMT and the matrix metalloproteinase gene ADAMTS14 in normal colonic mucosa of CRC patients. This suggested the existence of an epigenetic field defect for cancerization disrupting the methylation patterns of several loci, including MGMT or ADAMTS14, that may lead to predictive biomarkers for CRC. Methylation of these loci in normal mucosa was more frequent in elder (p = 0. 001) patients, and particularly in African Americans (p = 1 × 10-5), thus providing a possible mechanistic link between somatic epigenetic alterations and CRC racial disparities in North America.
Note: Altres ajuts: National Institutes of Health Grant R37CA63585, RO1CA83017 i RO1CA157328
Note: Número d'acord de subvenció MSSSI/FIS PI09/2444
Note: Número d'acord de subvenció MSSSI/FIS PI12/00511
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: KRAS mutations ; TP53 mutations ; MGMT ; O6-methylguanine-DNA methyltransferase ; ADAMTS14 ; CRC ; Colorectal cancer
Published in: Oncotarget, Vol. 6 Núm. 5 (february 2015) , ISSN 1949-2553

DOI: 10.18632/oncotarget.2852
PMID: 25638164


12 p, 5.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles

 Record created 2016-07-26, last modified 2020-08-15



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