Dataset Information

LINE-1 hypomethylation is neither present in rectal aberrant crypt foci nor associated with field defect in sporadic colorectal neoplasia.

ABSTRACT:

Background

Aberrant crypt foci (ACF) are considered the first identifiable preneoplastic lesion in colorectal cancer (CRC), and have been proposed as a potential biomarker for CRC risk. Global DNA hypomethylation is an early event in colorectal carcinogenesis, and long interspersed nuclear element-1 (LINE-1) methylation status is a well-known surrogate marker for genome-wide DNA methylation levels. Despite the gradual increase in DNA hypomethylation in the adenoma-carcinoma sequence, LINE-1 methylation in ACF has never been studied. Moreover, recent studies have reported a field defect for LINE-1 hypomethylation, suggesting that LINE-1 methylation status in normal mucosa could be used to stratify CRC risk and tailor preventive strategies. Thus, we assessed LINE-1 status by pyrosequencing in rectal ACF and paired normal colorectal mucosa from individuals with sporadic colon cancer (CC) (n = 35) or adenoma (n = 42), and from healthy controls (n = 70).

Findings

Compared with normal mucosa, LINE-1 in ACF were hypermethylated across all groups (P?ConclusionsOverall, our results suggest that global hypomethylation is not present in rectal ACF and argues against the existence of LINE-1 methylation field defect in sporadic colon cancer.

SUBMITTER: Quintanilla I

PROVIDER: S-EPMC4391726 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

LINE-1 hypomethylation is neither present in rectal aberrant crypt foci nor associated with field defect in sporadic colorectal neoplasia.

Quintanilla Isabel I Lopez-Cerón Maria M Jimeno Mireya M Cuatrecasas Miriam M Muñoz Jennifer J Moreira Leticia L Carballal Sabela S Leoz Maria Liz ML Camps Jordi J Castells Antoni A Pellisé Maria M Balaguer Francesc F

Clinical epigenetics 20141110 1

<h4>Background</h4>Aberrant crypt foci (ACF) are considered the first identifiable preneoplastic lesion in colorectal cancer (CRC), and have been proposed as a potential biomarker for CRC risk. Global DNA hypomethylation is an early event in colorectal carcinogenesis, and long interspersed nuclear element-1 (LINE-1) methylation status is a well-known surrogate marker for genome-wide DNA methylation levels. Despite the gradual increase in DNA hypomethylation in the adenoma-carcinoma sequence, LIN ...[more]

PMID: 25859284

Similar Datasets

Project description:Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion found within the human colon. Despite their relatively high frequency in the distal colon, few studies have examined the molecular characteristics of ACF within the proximal colon. In the following study, clinical participants (n = 184) were screened for ACF using high-definition chromoendoscopy with contrast dye-spray. Following pathologic confirmation, ACF biopsies were subjected to laser capture microdissection (LCM), and epithelial cells were evaluated for somatic mutations with a customized colorectal cancer mutation panel using DNA-mass spectrometry. Samples were further characterized for microsatellite instability (MSI). Logistic models were used to associate proximal ACF with synchronous (detected during the same procedure) neoplasia. Thirty-nine percent of participants had at least one histologically confirmed proximal ACF. Individuals with a proximal ACF were significantly more likely to present with a synchronous neoplasm (P = 0.001), and specifically, a proximal, tubular, or tubulovillous adenoma (multivariable OR = 2.69; 95% confidence interval, 1.12-6.47; P = 0.027). Proximal ACF were more likely to be dysplastic (52%) compared with distal ACF (13%; P < 0.0001). Somatic mutations to APC, BRAF, KRAS, NRAS, and ERBB2 were detected in 37% of proximal ACF. Hyperplastic ACF were more often MSI-high, but there were no differences in MSI status observed by colonic location. In summary, ACF are identified in the proximal colons of approximately 40% of individuals undergoing chromoendoscopy and more often in patients with synchronous proximal adenomas.Implications: This study provides the most complete set of data, to date, that ACF represent the earliest step in the adenoma-carcinoma sequence but remain below the detection limit of conventional endoscopy.Visual Overview: http//mcr.accrjournals.org/content/molcanres/16/3/486/F1.large.jpg Mol Cancer Res; 16(3); 486-95. ©2017 AACR.

Dataset Information

LINE-1 hypomethylation is neither present in rectal aberrant crypt foci nor associated with field defect in sporadic colorectal neoplasia.

Background

Findings

Publications

LINE-1 hypomethylation is neither present in rectal aberrant crypt foci nor associated with field defect in sporadic colorectal neoplasia.

Similar Datasets

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