title: BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer.
abstract: Mucinous colorectal cancer (CRC) has been reported to have distinct clinicopathological and genetic characteristics. However, the incidence and the relationship among microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and BRAF and KRAS mutations in mucinous and non-mucinous CRC are not known. Activating mutations of BRAF and KRAS and their relationship with MSI and CIMP were examined in 83 sporadic CRC specimens (26 mucinous and 57 non-mucinous CRC). MSI, CIMP, BRAF and KRAS mutation were observed in 17, 24, 25 and 36% of the tumors, respectively. BRAF mutation was highly correlated with MSI (p < 0.001) and CIMP (p < 0.001). A higher incidence of MSI (27% vs. 12%), CIMP (38% vs. 18%, p < 0.05) and BRAF mutation (46% vs. 16%, p < 0.01) was observed in mucinous CRC. KRAS mutation (27% vs. 40%) was observed more frequently in non-mucinous CRC. Significantly higher percentages of mucinous CRC (54%, p < 0.05) had MSI or CIMP or BRAF mutations. Concordant occurrence of 2 or more of these alterations was observed in 39% of mucinous CRC and only 11% of non-mucinous CRC (p < 0.01). The more frequent occurrence and closer association among MSI, CIMP and BRAF mutation in mucinous CRC observed in our study further supports the idea that its pathogenesis may involve distinct genetic and epigenetic changes.
authors.affiliation: Department of Medicine, Gastrointestinal Research Laboratory, Veterans Affairs Medical Center, University of California San Francisco, San Francisco, CA 94121, USA.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kakar
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kim
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
authors.forename: Marvin H
authors.initials: MH
authors.lastname: Sleisenger
authors.forename: Young S
authors.initials: YS
authors.lastname: Kim
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005260:Female; D042822:Genomic Instability; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf