@article{0139d6b7e15d45ec82614439988b3c3b,
title = "Methylation in p14ARF is frequently observed in colorectal cancer with low-level microsatellite instability",
abstract = "Colorectal cancer (CRC) can be classified as high-level microsatellite instability (MSI-H), low-level MSI (MSI-L) and microsatellite stable (MSS) depending on levels of MSI. MSI-H CRC relies on a distinct molecular pathway due to the mismatch repair (MMR) deficiency and shows methylation in multiple gene promoters. The genetic pathway leading to MSI-L is unknown, although higher levels of promoter methylation are observed in this group compared with MSS CRCs. This study explored how promoter methylation affects MSI phenotype, by analysing the methylation status of eight CRC-related promoters, MSI phenotype and KRAS/BRAF mutations in a series of 234 CRCs. Promoter methylation of p14ARF was significantly related to MSI-L CRC with KRAS mutation. The MSI-H phenotype was related to methylation of MLH1 as expected, while the MSS phenotype was related to methylation of p16INK4a and O 6-methylguanine-DNA methyltransferase, although this was not statistically significant. Thus, promoter methylation of p14ARF could be a significant alteration leading to CRC with MSI-L.",
keywords = "Colorectal cancer, Methylation, Microsatellite instability, p14",
author = "K. Kominami and T. Nagasaka and Cullings, {H. M.} and N. Hoshizima and H. Sasamoto and J. Young and Leggett, {B. A.} and N. Tanaka and Nagahide Matsubara",
note = "Funding Information: p14 ARF is Frequently Observed in Colorectal Cancer with Low-level Microsatellite Instability Kominami K 1 Nagasaka T 1 Cullings HM 2 Hoshizima N 1 Sasamoto H 1 Young J 3 Leggett BA 3 Tanaka N 1 Matsubara N 1 1 Department of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan 2 Department of Statistics, Radiation Effects Research Foundation, Hiroshima, Japan 3 Division of Cancer and Cell Biology, Queensland Institute of Medical Research, Herston, Queensland, Australia Author's address for correspondence Dr Nagahide Matsubara Department of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. E-mail: nagamb@cc.okayama-u.ac.jp 8 2009 37 4 1038 1045 12 12 2008 6 1 2009 11 6 2009 {\textcopyright} 2009 SAGE Publications 2009 SAGE Publications Colorectal cancer (CRC) can be classified as high-level microsatellite instability (MSI-H), low-level MSI (MSI-L) and microsatellite stable (MSS) depending on levels of MSI. MSI-H CRC relies on a distinct molecular pathway due to the mismatch repair (MMR) deficiency and shows methylation in multiple gene promoters. The genetic pathway leading to MSI-L is unknown, although higher levels of promoter methylation are observed in this group compared with MSS CRCs. This study explored how promoter methylation affects MSI phenotype, by analysing the methylation status of eight CRC-related promoters, MSI phenotype and KRAS/BRAF mutations in a series of 234 CRCs. Promoter methylation of p14 ARF was significantly related to MSI-L CRC with KRAS mutation. The MSI-H phenotype was related to methylation of MLH1 as expected, while the MSS phenotype was related to methylation of p16 INK4a and O 6 -methylguanine-DNA methyltransferase , although this was not statistically significant. Thus, promoter methylation of p14 ARF could be a significant alteration leading to CRC with MSI-L. Colorectal cancer Methylation p14 Microsatellite instability ",
year = "2009",
doi = "10.1177/147323000903700408",
language = "English",
volume = "37",
pages = "1038--1045",
journal = "Journal of International Medical Research",
issn = "0300-0605",
publisher = "Field House Publishing LLP",
number = "4",
}
