title: Molecular differences in the microsatellite stable phenotype between left-sided and right-sided colorectal cancer.
abstract: Differences in the pathogenesis of microsatellite stable (MSS) sporadic colorectal cancers (CRCs) between left-sided CRC (LC) and right-sided CRC (RC) have not been clarified. To identify pathogenesis-related genomic differences between MSS CRCs within the two locations, we performed a comprehensive molecular analysis using crypt isolation with samples from 92 sporadic CRCs. Microsatellite instability (MSI; high and low/negative) and DNA methylation status (low methylation epigenome; intermediate methylation epigenome [IME] or high methylation epigenome [HME]) were determined using polymerase chain reaction (PCR) microsatellite analysis and PCR-bisulfite pyrosequencing, respectively. Additionally, mutations in the TP53, KRAS, BRAF and PIK3CA genes were examined using PCR-bisulfite pyrosequencing (for KRAS and BRAF mutations) or PCR-single conformation polymorphism (for TP53 and PIK3CA mutations), followed by sequencing of aberrant bands. Finally, a genome-wide study using a copy number alteration (CNA)-targeted single nucleotide polymorphism array was performed. Ninety-two CRCs were classified into 71 MSS and 21 MSI phenotypes. We examined 71 CRCs with the MSS phenotype (LC, 56; RC, 15). Mutations in KRAS were associated with RC with the MSS phenotype, whereas mutations in TP53 were more frequently found in LC with the MSS phenotype. There were significant differences in the frequencies of KRAS and TP53 mutations in the IME between LC and RC with the MSS phenotype. Although CNA gains were associated with LC with the MSS phenotype, CNA losses were not major alterations associated with the MSS phenotype. These findings suggested that the molecular pathogenesis of the MSS phenotype in LC was different from that in RC.
authors: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan.|Department of Surgery, Tohoku University Tohoku Graduate School of Medicine, 1-1, Aoba-ku, Sendai, 980-8574, Japan.
authors: Yayoi
authors: Y
authors: Takahashi
authors: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan. tsugai@iwate-med.ac.jp.
authors: Tamotsu
authors: T
authors: Sugai
authors: Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University, 1-1, Yahaba, Morioka, 028-3694, Japan.
authors: Wataru
authors: W
authors: Habano
authors: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan.
authors: Kazuyuki
authors: K
authors: Ishida
authors: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan.
authors: Makoto
authors: M
authors: Eizuka
authors: Department of Surgery, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan.
authors: Koki
authors: K
authors: Otsuka
authors: Department of Surgery, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan.
authors: Akira
authors: A
authors: Sasaki
authors: Division of Gastroenterology, Department of Internal Medicine, 19-1, Uchimaru, Morioka, 020-8505, Japan.
authors: Takayuki Matsumoto
authors: Department of Surgery, Tohoku University Tohoku Graduate School of Medicine, 1-1, Aoba-ku, Sendai, 980-8574, Japan.
authors: Takanori
authors: T
authors: Morikawa
authors: Department of Surgery, Tohoku University Tohoku Graduate School of Medicine, 1-1, Aoba-ku, Sendai, 980-8574, Japan.
authors: Michiaki
authors: M
authors: Unno
authors: Department of Molecular Biology, Sapporo Medical University School of Medicine, S1 W17, Chuo-ku, Sapporo, 060-8556, Japan.
authors: Hiromu
authors: H
authors: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002877:Chromosomes, Human; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010641:Phenotype
keywords: colorectal cancer; copy number alteration; microsatellite stable; mutation; tumor location