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Title: A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer
Author: Antelo, Marina
Balaguer Prunés, Francesc
Shia, Jinru
Shen, Yan
Hur, Keun
Moreira, Leticia
Cuatrecasas Freixas, Miriam
Bujanda, Luis
Giraldez, Maria Dolores
Takahashi, Masanobu
Cabanne, Ana
Barugel, Mario Edmundo
Arnold, Mildred
Roca, Enrique Luis
Andreu, Montserrat
Castellví Bel, Sergi
Llor, Xavier
Jover, Rodrigo
Castells Garangou, Antoni
Boland, C. Richard
Goel, Ajay
Keywords: Càncer colorectal
Epidemiologia genètica
Colorectal cancer
Genetic epidemiology
Issue Date: 25-Sep-2012
Publisher: Public Library of Science (PLoS)
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.
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It is part of: PLoS One, 2012, vol. 7, num. 9, p. e45357
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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