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MicroRNA‐31 expression in relation to BRAF mutation, CpG island methylation and colorectal continuum in serrated lesions
Author(s) -
Ito Miki,
Mitsuhashi Kei,
Igarashi Hisayoshi,
Nosho Katsuhiko,
Naito Takafumi,
Yoshii Shinji,
Takahashi Hiroaki,
Fujita Masahiro,
Sukawa Yasutaka,
Yamamoto Eiichiro,
Takahashi Taiga,
Adachi Yasushi,
Nojima Masanori,
Sasaki Yasushi,
Tokino Takashi,
Baba Yoshifumi,
Maruyama Reo,
Suzuki Hiromu,
Imai Kohzoh,
Yamamoto Hiroyuki,
Shinomura Yasuhisa
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28920
Subject(s) - cancer research , microsatellite instability , mlh1 , dna methylation , dysplasia , rectum , biology , mutation , epigenetics , methylation , cpg site , colorectal cancer , microrna , pathology , medicine , oncology , cancer , genetics , dna mismatch repair , gene expression , gene , allele , microsatellite
The CpG island methylator phenotype (CIMP) is a distinct form of epigenomic instability. Many CIMP‐high colorectal cancers (CRCs) with BRAF mutation are considered to arise from serrated pathway. We recently reported that microRNA‐31 (miR‐31) is associated with BRAF mutation in colorectal tumors. Emerging new approaches have revealed gradual changes in BRAF mutation and CIMP‐high throughout the colorectum in CRCs. Here, we attempted to identify a possible association between miR‐31 and epigenetic features in serrated pathway, and hypothesized that miR‐31 supports the “colorectal continuum” concept. We evaluated miR‐31 expression, BRAF mutation and epigenetic features including CIMP status in 381 serrated lesions and 222 non‐serrated adenomas and examined associations between them and tumor location (rectum; sigmoid, descending, transverse and ascending colon and cecum). A significant association was observed between high miR‐31 expression and CIMP‐high status in serrated lesions with BRAF mutation ( p = 0.0001). In contrast, miR‐31 was slightly but insignificantly associated with CIMP status in the cases with wild‐type BRAF . miR‐31 expression in sessile serrated adenomas (SSAs) with cytological dysplasia was higher than that in SSAs, whereas, no significant difference was observed between traditional serrated adenomas (TSAs) and TSAs with high‐grade dysplasia. The frequency of miR‐31, BRAF mutation CIMP‐high and MLH1 methylation increased gradually from the rectum to cecum in serrated lesions. In conclusion, miR‐31 expression was associated with CIMP‐high status in serrated lesions with BRAF mutation. Our data also suggested that miR‐31 plays an important role in SSA evolution and may be a molecule supporting the colorectal continuum.