A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps

A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps

A subset of colorectal cancers (CRCs) harbor the CpG island methylator phenotype (CIMP), with concurrent multiple promoter hypermethylation of tumor-related genes. A serrated pathway in which CIMP is developed from serrated polyps is proposed. The present study characterized CIMP and morphologically...

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Main Authors: HOKAZONO, KOJI, UEKI, TAKASHI, NAGAYOSHI, KINUKO, NISHIOKA, YASUNOBU, HATAE, TATSUNOBU, KOGA, YUTAKA, HIRAHASHI, MINAKO, ODA, YOSHINAO, TANAKA, MASAO
Format: Online
Language:English
Published: D.A. Spandidos 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186580/
id pubmed-4186580
recordtype oai_dc
spelling pubmed-41865802014-10-06 A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps HOKAZONO, KOJI UEKI, TAKASHI NAGAYOSHI, KINUKO NISHIOKA, YASUNOBU HATAE, TATSUNOBU KOGA, YUTAKA HIRAHASHI, MINAKO ODA, YOSHINAO TANAKA, MASAO Articles A subset of colorectal cancers (CRCs) harbor the CpG island methylator phenotype (CIMP), with concurrent multiple promoter hypermethylation of tumor-related genes. A serrated pathway in which CIMP is developed from serrated polyps is proposed. The present study characterized CIMP and morphologically examined precursor lesions of CIMP. In total, 104 CRCs treated between January 1996 and December 2004 were examined. Aberrant promoter methylation of 15 cancer-related genes was analyzed. CIMP status was classified according to the number of methylated genes and was correlated with the clinicopathological features, including the concomitant polyps in and around the tumors. The frequency of aberrant methylation in each CRC showed a bimodal pattern, and the CRCs were classified as CIMP-high (CIMP-H), CIMP-low (CIMP-L) and CIMP-negative (CIMP-N). CIMP-H was associated with aberrant methylation of MLH1 (P=0.005) and with an improved recurrence-free survival (RFS) rate following curative resection compared with CIMP-L/N (five-year RFS rate, 93.8 vs. 67.1%; P=0.044), while CIMP-N tumors were associated with frequent distant metastases at diagnosis (P=0.023). No concomitant serrated lesions were present in the tumors, whereas conventional adenoma was contiguous with 11 (10.6%) of 104 CRCs, including four CIMP-H CRCs. CIMP-H was classified in CRCs by a novel CIMP marker panel and the presence of concomitant tumors revealed that certain CIMP-H CRCs may have arisen from conventional adenomas. D.A. Spandidos 2014-11 2014-08-08 /pmc/articles/PMC4186580/ /pubmed/25289081 http://dx.doi.org/10.3892/ol.2014.2430 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author HOKAZONO, KOJI
UEKI, TAKASHI
NAGAYOSHI, KINUKO
NISHIOKA, YASUNOBU
HATAE, TATSUNOBU
KOGA, YUTAKA
HIRAHASHI, MINAKO
ODA, YOSHINAO
TANAKA, MASAO
spellingShingle HOKAZONO, KOJI
UEKI, TAKASHI
NAGAYOSHI, KINUKO
NISHIOKA, YASUNOBU
HATAE, TATSUNOBU
KOGA, YUTAKA
HIRAHASHI, MINAKO
ODA, YOSHINAO
TANAKA, MASAO
A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps
author_facet HOKAZONO, KOJI
UEKI, TAKASHI
NAGAYOSHI, KINUKO
NISHIOKA, YASUNOBU
HATAE, TATSUNOBU
KOGA, YUTAKA
HIRAHASHI, MINAKO
ODA, YOSHINAO
TANAKA, MASAO
author_sort HOKAZONO, KOJI
title A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps
title_short A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps
title_full A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps
title_fullStr A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps
title_full_unstemmed A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps
title_sort cpg island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps
description A subset of colorectal cancers (CRCs) harbor the CpG island methylator phenotype (CIMP), with concurrent multiple promoter hypermethylation of tumor-related genes. A serrated pathway in which CIMP is developed from serrated polyps is proposed. The present study characterized CIMP and morphologically examined precursor lesions of CIMP. In total, 104 CRCs treated between January 1996 and December 2004 were examined. Aberrant promoter methylation of 15 cancer-related genes was analyzed. CIMP status was classified according to the number of methylated genes and was correlated with the clinicopathological features, including the concomitant polyps in and around the tumors. The frequency of aberrant methylation in each CRC showed a bimodal pattern, and the CRCs were classified as CIMP-high (CIMP-H), CIMP-low (CIMP-L) and CIMP-negative (CIMP-N). CIMP-H was associated with aberrant methylation of MLH1 (P=0.005) and with an improved recurrence-free survival (RFS) rate following curative resection compared with CIMP-L/N (five-year RFS rate, 93.8 vs. 67.1%; P=0.044), while CIMP-N tumors were associated with frequent distant metastases at diagnosis (P=0.023). No concomitant serrated lesions were present in the tumors, whereas conventional adenoma was contiguous with 11 (10.6%) of 104 CRCs, including four CIMP-H CRCs. CIMP-H was classified in CRCs by a novel CIMP marker panel and the presence of concomitant tumors revealed that certain CIMP-H CRCs may have arisen from conventional adenomas.
publisher D.A. Spandidos
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186580/
_version_ 1613141234323292160

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