title: MicroRNA-31 expression in relation to BRAF mutation, CpG island methylation and colorectal continuum in serrated lesions.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ito
authors.forename: Kei
authors.initials: K
authors.lastname: Mitsuhashi
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Igarashi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nosho
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Shinji
authors.initials: S
authors.lastname: Yoshii
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Sukawa
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Taiga
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Masanori
authors.initials: M
authors.lastname: Nojima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokino
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Baba
authors.forename: Reo
authors.initials: R
authors.lastname: Maruyama
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D010641:Phenotype; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: C534612:MIRN31 microRNA, human; D035683:MicroRNAs; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; CIMP; colon; miR-31; serrated polyp