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A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer

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Title: A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer
Author(s): Antelo, Marina; Balaguer, Francesc; Shia, Jinru; Shen, Yan; Hur, Keun; Moreira, Leticia; Cuatrecasas, Miriam; Bujanda, Luis; Giraldez, Maria Dolores; Takahashi, Masanobu; Cabanne, Ana; Barugel, Mario Edmundo; Arnold, Mildred; Roca, Enrique Luis; Andreu, Montserrat; Castellvi- Bel, Sergi; Llor, Xavier; Jover, Rodrigo; Castells, Antoni; Boland, C. Richard; Goel, Ajay
Abstract: Objective: Early-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously. Design: We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed <= 50 years old (n = 188), a group of sporadic CRC >50 years (MSS n = 89; MSI n = 46), and a group of Lynch syndrome CRCs (n = 20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated. Results: Mean LINE-1 methylation levels (+/- SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001). Compared to patients with <65% LINE-1 methylation in tumors, those with >= 65% LINE-1 methylation had significantly better overall survival (p = 0.026, log rank test). Conclusions: LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC.
Issue Date: 2012-09
Publisher: Public Library of Science
Citation Info: Antelo M, Balaguer F, Shia J, Shen Y, Hur K, et al. (2012) A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer. PLoS ONE 7(9): e45357. doi:10.1371/journal.pone.0045357
Type: Article
Description: © 2012 Antelo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The original version is available through Public Library of Science at DOI: 10.1371/journal.pone.0045357.
URI: http://hdl.handle.net/10027/10773
ISSN: 1932-6203
Sponsor: The present work was supported by grants R01 CA72851 and CA129286 from the National Cancer Institute, National Institutes of Health; and funds from the Baylor Research Institute to CRB and AG. FB was supported by a grant from Fundacio´n Alfonso Martı´n Escudero and from Instituto de Salud Carlos III (PI10/00384). MA was supported by a ‘‘Type I Postgraduate Scholarship’’ given by the CONICET (National Council of Scientific and Technical Investigations) dependent on the Argentine Ministry of Science and Technology.
Date Available in INDIGO: 2013-12-03
 

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