Methylation in p14(ARF) is frequently observed in colorectal cancer with low-level microsatellite instability.
J Int Med Res
; 37(4): 1038-45, 2009.
Article
in En
| MEDLINE
| ID: mdl-19761686
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 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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
DNA Methylation
/
Gene Silencing
/
Tumor Suppressor Protein p14ARF
/
Microsatellite Instability
Limits:
Humans
Language:
En
Journal:
J Int Med Res
Year:
2009
Type:
Article
Affiliation country:
Japan