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Cancer Prev Res (Phila). 2013 Jul;6(7):656-65. doi: 10.1158/1940-6207.CAPR-12-0501. Epub 2013 May 21.

DNA methylation biomarkers for noninvasive diagnosis of colorectal cancer.

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  • 1Cancer Epigenetics and Biology Program (PEBC), Catalan Institute of Oncology (ICO-IDIBELL), Barcelona 08908, Spain.

Abstract

DNA methylation biomarkers for noninvasive diagnosis of colorectal cancer (CRC) and precursor lesions have been extensively studied. Different panels have been reported attempting to improve current protocols in clinical practice, although no definite biomarkers have been established. In the present study, we have examined patient biopsies starting from a comprehensive analysis of DNA methylation differences between paired normal and tumor samples in known cancer-related genes aiming to select the best performing candidates informative for CRC diagnosis in stool samples. Five selected markers were considered for subsequent analyses in independent biologic cohorts and in silico data sets. Among the five selected genes, three of them (AGTR1, WNT2 and SLIT2) were validated in stool DNA of affected patients with a detection sensitivity of 78% [95% confidence interval (CI), 56%-89%]. As a reference, DNA methylation of VIM and SEPT9 was evaluated in a subset of stool samples yielding sensitivities of 55% and 20%, respectively. Moreover, our panel may complement histologic and endoscopic diagnosis of inflammatory bowel disease (IBD)-associated neoplasia, as it was also efficient detecting aberrant DNA methylation in non-neoplastic tissue samples from affected patients. This novel panel of specific methylation markers can be useful for early diagnosis of CRC using stool DNA and may help in the follow-up of high-risk patients with IBD.

©2013 AACR.

PMID:
23694962
[PubMed - indexed for MEDLINE]
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