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DNA methylation epigenotype and clinical features of NRAS‐mutation(+) colorectal cancer
Sporadic colorectal cancer (CRC) is classified into several molecular subtypes. We previously established two groups of DNA methylation markers through genome‐wide DNA methylation analysis to classify CRC into distinct subgroups: high‐, intermediate‐, and low‐methylation epigenotypes (HME, IME, and...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430106/ https://www.ncbi.nlm.nih.gov/pubmed/28378457 http://dx.doi.org/10.1002/cam4.1061 |
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author | Takane, Kiyoko Akagi, Kiwamu Fukuyo, Masaki Yagi, Koichi Takayama, Tadatoshi Kaneda, Atsushi |
author_facet | Takane, Kiyoko Akagi, Kiwamu Fukuyo, Masaki Yagi, Koichi Takayama, Tadatoshi Kaneda, Atsushi |
author_sort | Takane, Kiyoko |
collection | PubMed |
description | Sporadic colorectal cancer (CRC) is classified into several molecular subtypes. We previously established two groups of DNA methylation markers through genome‐wide DNA methylation analysis to classify CRC into distinct subgroups: high‐, intermediate‐, and low‐methylation epigenotypes (HME, IME, and LME, respectively). HME CRC, also called CpG island methylator phenotype (CIMP)‐high CRC, shows methylation of both Group 1 markers (CIMP markers) and Group 2 markers, while IME/CIMP‐low CRC shows methylation of Group 2, but not of Group 1 markers, and LME CRC shows no methylation of either Group 1 or Group 2 markers. While BRAF‐ and KRAS‐mutation(+) CRC strongly correlated with HME and IME, respectively, clinicopathological features of NRAS‐mutation(+) CRC, including association with DNA methylation, remain unclear. To characterize NRAS‐mutation(+) CRC, the methylation levels of 19 methylation marker genes (6 Group 1 and 13 Group 2) were analyzed in 61 NRAS‐mutation(+) and 144 NRAS‐mutation(−) CRC cases by pyrosequencing, and their correlation with clinicopathological features was investigated. Different from KRAS‐mutation(+) CRC,NRAS‐mutation(+) CRC significantly correlated with LME. NRAS‐mutation(+) CRC showed significantly better prognosis than KRAS‐mutation(+) CRC (P = 3 × 10(−4)). NRAS‐mutation(+) CRC preferentially occurred in elder patients (P = 0.02) and at the distal colon (P = 0.006), showed significantly less lymph vessel invasion (P = 0.002), and correlated with LME (P = 8 × 10(−5)). DNA methylation significantly accumulated at the proximal colon. NRAS‐mutation(+) CRC may constitute a different subgroup from KRAS‐mutation(+) CRC, showing significant correlation with LME, older age, distal colon, and relatively better prognosis. |
format | Online Article Text |
id | pubmed-5430106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54301062017-05-17 DNA methylation epigenotype and clinical features of NRAS‐mutation(+) colorectal cancer Takane, Kiyoko Akagi, Kiwamu Fukuyo, Masaki Yagi, Koichi Takayama, Tadatoshi Kaneda, Atsushi Cancer Med Clinical Cancer Research Sporadic colorectal cancer (CRC) is classified into several molecular subtypes. We previously established two groups of DNA methylation markers through genome‐wide DNA methylation analysis to classify CRC into distinct subgroups: high‐, intermediate‐, and low‐methylation epigenotypes (HME, IME, and LME, respectively). HME CRC, also called CpG island methylator phenotype (CIMP)‐high CRC, shows methylation of both Group 1 markers (CIMP markers) and Group 2 markers, while IME/CIMP‐low CRC shows methylation of Group 2, but not of Group 1 markers, and LME CRC shows no methylation of either Group 1 or Group 2 markers. While BRAF‐ and KRAS‐mutation(+) CRC strongly correlated with HME and IME, respectively, clinicopathological features of NRAS‐mutation(+) CRC, including association with DNA methylation, remain unclear. To characterize NRAS‐mutation(+) CRC, the methylation levels of 19 methylation marker genes (6 Group 1 and 13 Group 2) were analyzed in 61 NRAS‐mutation(+) and 144 NRAS‐mutation(−) CRC cases by pyrosequencing, and their correlation with clinicopathological features was investigated. Different from KRAS‐mutation(+) CRC,NRAS‐mutation(+) CRC significantly correlated with LME. NRAS‐mutation(+) CRC showed significantly better prognosis than KRAS‐mutation(+) CRC (P = 3 × 10(−4)). NRAS‐mutation(+) CRC preferentially occurred in elder patients (P = 0.02) and at the distal colon (P = 0.006), showed significantly less lymph vessel invasion (P = 0.002), and correlated with LME (P = 8 × 10(−5)). DNA methylation significantly accumulated at the proximal colon. NRAS‐mutation(+) CRC may constitute a different subgroup from KRAS‐mutation(+) CRC, showing significant correlation with LME, older age, distal colon, and relatively better prognosis. John Wiley and Sons Inc. 2017-04-04 /pmc/articles/PMC5430106/ /pubmed/28378457 http://dx.doi.org/10.1002/cam4.1061 Text en © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Cancer Research Takane, Kiyoko Akagi, Kiwamu Fukuyo, Masaki Yagi, Koichi Takayama, Tadatoshi Kaneda, Atsushi DNA methylation epigenotype and clinical features of NRAS‐mutation(+) colorectal cancer |
title |
DNA methylation epigenotype and clinical features of NRAS‐mutation(+) colorectal cancer |
title_full |
DNA methylation epigenotype and clinical features of NRAS‐mutation(+) colorectal cancer |
title_fullStr |
DNA methylation epigenotype and clinical features of NRAS‐mutation(+) colorectal cancer |
title_full_unstemmed |
DNA methylation epigenotype and clinical features of NRAS‐mutation(+) colorectal cancer |
title_short |
DNA methylation epigenotype and clinical features of NRAS‐mutation(+) colorectal cancer |
title_sort | dna methylation epigenotype and clinical features of nras‐mutation(+) colorectal cancer |
topic | Clinical Cancer Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430106/ https://www.ncbi.nlm.nih.gov/pubmed/28378457 http://dx.doi.org/10.1002/cam4.1061 |
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