title: Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations.
abstract: To clarify the molecular and clinicopathological characteristics of colorectal serrated lesions, we assessed the DNA methylation of cancer-associated genes in a cohort of BRAF-mutant precancerous lesions from 94 individuals. We then compared those results with the lesions' clinicopathological features, especially colorectal subsites. The lesions included hyperplastic polyps (n = 16), traditional serrated adenomas (TSAs) (n = 15), TSAs with sessile serrated adenomas (SSAs) (n = 6), SSAs (n = 49) and SSAs with dysplasia (n = 16). The prevalence of lesions exhibiting the CpG island methylator phenotype (CIMP) was lower in the sigmoid colon and rectum than in other bowel subsites, including the cecum, ascending, transverse and descending colon. In addition, several cancer-associated genes showed higher methylation levels within lesions in the proximal to sigmoid colon than in the sigmoid colon and rectum. These results indicate that the methylation status of lesions with BRAF mutation is strongly associated with their location, histological findings and neoplastic pathways. By contrast, no difference in aberrant DNA methylation was observed in normal-appearing background colonic mucosa along the bowel subsites, which may indicate the absence of an epigenetic field defect.
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Advanced Research in Community Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sawada
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Hiro-O
authors.initials: HO
authors.lastname: Yamano
authors.affiliation: Center for Translational Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nojima
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Reo
authors.initials: R
authors.lastname: Maruyama
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Ashida
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Aoki
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Hiro-O
authors.initials: HO
authors.lastname: Matsushita
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Harada
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Wakita
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Niinuma
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kai
authors.affiliation: Department of Molecular Diagnostic Pathology, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Eizuka
authors.affiliation: Department of Molecular Diagnostic Pathology, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; CpG island methylator phenotype; colorectal cancer; methylation; serrated lesion