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

作者：Antelo Marina; Balaguer Francesc^*; Shia Jinru; Shen Yan; Hur Keun; Moreira Leticia; Cuatrecasas Miriam; Bujanda Luis; Dolores Giraldez Maria; Takahashi Masanobu; Cabanne Ana; Edmundo Barugel Mario; Arnold Mildred; Luis Roca Enrique; Andreu Montserrat; Castellvi Bel Sergi; Llor Xavier; Jover Rodrigo; Castells Antoni; Boland C Richard; Goel Ajay

来源：PLos One, 2012, 7(9): e45357.

DOI：10.1371/journal.pone.0045357

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. %26lt;br%26gt;Design: We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed %26lt;= 50 years old (n = 188), a group of sporadic CRC %26gt;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. %26lt;br%26gt;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%26lt;0.0001). Compared to patients with %26lt;65% LINE-1 methylation in tumors, those with %26gt;= 65% LINE-1 methylation had significantly better overall survival (p = 0.026, log rank test). %26lt;br%26gt;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.

• 出版日期2012-9-25