title: Analysis of molecular alterations in left- and right-sided colorectal carcinomas reveals distinct pathways of carcinogenesis: proposal for new molecular profile of colorectal carcinomas.
abstract: To clarify distinct genetic profiles of colorectal cancers based on tumor location (left- and right-sided), we evaluated the status of loss of heterozygosity (LOH), CpG islands methylation phenotype (CIMP), microsatellite instability (MSI), and mutations of p53, Ki-ras, and APC genes in 119 colorectal cancers. Statuses of LOH (at 5q, 8p, 17p, 18q, and 22q), MSI, and CIMP (MINT1, MINT2, MINT31, MLH-1, MGMT, p14, p16, and RASSF1A) were determined using microsatellite polymerase chain reaction and methylation-specific polymerase chain reaction coupled with a crypt isolation method, respectively. In addition, mutations of p53, Ki-ras, and APC genes were also examined. LOH, MSI, and CIMP status allowed us to classify samples into two groups: low or negative and high or positive. Whereas the frequency of p53 mutations in the LOH-high status was significantly higher in left-sided cancers than in right-sided cancers, CIMP-high in the LOH-high status and MSI-positive status were more frequently found in right-sided cancers compared with left-sided cancers. Finally, location-specific methylated loci were seen in colorectal cancers: type I (dominant in right-sided cancer) and type II (common in both segments of cancer). Our data confirm that distinct molecular pathways to colorectal cancer dominate in the left and right sides of the bowel.
authors.affiliation: Division of Pathology, Central Clinical Laboratory, Iwate Medical University, 19-1 Morioka, 020-8505, Japan. tsugai@cocoa.ocn.ne.jp
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.forename: Wataru
authors.initials: W
authors.lastname: Habano
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Jiao
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Tsukahara
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Takeda
authors.forename: Koki
authors.initials: K
authors.lastname: Otsuka
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D017491:Genes, APC; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53