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

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    Date
    2012-09
    Author
    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
    Publisher
    Public Library of Science
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    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.
    Type
    Article
    Date available in INDIGO
    2013-12-03T22:30:39Z
    URI
    http://hdl.handle.net/10027/10773
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    • Publications -Medicine

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