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2012-09-25

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cc-by (c) Antelo, Marina et al., 2012
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/124828

A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer

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https://doi.org/10.1371/journal.pone.0045357

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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.

Matèries

Càncer colorectal, Càncer, Epidemiologia genètica

Matèries (anglès)

Colorectal cancer, Cancer, Genetic epidemiology

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Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

ANTELO, Marina, BALAGUER PRUNÉS, Francesc, SHIA, Jinru, SHEN, Yan, HUR, Keun, MOREIRA RUIZ, 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. A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer. _PLoS One_. 2012. Vol. 7, núm. 9, pàgs. e45357. [consulta: 21 de gener de 2026]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/124828]

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