Methylation in p14ARF is frequently observed in colorectal cancer with low-level microsatellite instability

K. Kominami, T. Nagasaka, H. M. Cullings, N. Hoshizima, H. Sasamoto, J. Young, B. A. Leggett, N. Tanaka, Nagahide Matsubara

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1038-1045
Number of pages8
JournalJournal of International Medical Research
Volume37
Issue number4
DOIs
Publication statusPublished - 2009

Keywords

  • Colorectal cancer
  • Methylation
  • Microsatellite instability
  • p14

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biochemistry, medical

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    Kominami, K., Nagasaka, T., Cullings, H. M., Hoshizima, N., Sasamoto, H., Young, J., Leggett, B. A., Tanaka, N., & Matsubara, N. (2009). Methylation in p14ARF is frequently observed in colorectal cancer with low-level microsatellite instability. Journal of International Medical Research, 37(4), 1038-1045. https://doi.org/10.1177/147323000903700408