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Your search keyword '"Suemoto Yuko"' showing total 2 results
Start Over Author "Suemoto Yuko" Journal modern pathology an official journal of the united states and canadian academy of pathology inc
2 results on '"Suemoto Yuko"'

1. CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, but also low-level methylation at individual loci.

Author

Kawasaki T, Ohnishi M, Nosho K, Suemoto Y, Kirkner GJ, Meyerhardt JA, Fuchs CS, and Ogino S

Subjects
Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Biomarkers, Tumor, Calcium Channels, T-Type genetics, Calcium Channels, T-Type metabolism, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Core Binding Factor Alpha 3 Subunit genetics, Core Binding Factor Alpha 3 Subunit metabolism, Cyclin-Dependent Kinase Inhibitor p16 genetics, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Female, Humans, Insulin-Like Growth Factor II genetics, Insulin-Like Growth Factor II metabolism, Male, MutL Protein Homolog 1, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Nuclear Proteins genetics, Nuclear Proteins metabolism, Receptors, Retinoic Acid genetics, Receptors, Retinoic Acid metabolism, Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling Proteins genetics, Suppressor of Cytokine Signaling Proteins metabolism, Colorectal Neoplasms genetics, CpG Islands genetics, DNA Methylation, Gene Expression Regulation, Neoplastic
Abstract

The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct phenotype in colorectal cancer. However, the concept of CIMP-low with less extensive CpG island methylation is still evolving. Our aim is to examine whether density of methylation in individual CpG islands was different between CIMP-low and CIMP-high tumors. Utilizing MethyLight technology and 889 population-based colorectal cancers, we quantified DNA methylation (methylation index, percentage of methylated reference) at 14 CpG islands, including 8 CIMP-high-specific loci (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1). Methylation positivity in each locus was defined as methylation index>4. Low-level methylation (methylation index>0, <20) in each CIMP-high-specific locus was significantly more common in 340 CIMP-low tumors (1/8-5/8 methylation-positive loci) than 133 CIMP-high tumors (> or =6/8 methylation-positive loci) and 416 CIMP-0 tumors (0/8 methylation-positive loci) (P< or =0.002). In the other six loci (CHFR, HIC1, IGFBP3, MGMT, MINT31 and WRN), which were not highly specific for CIMP-high, low-level methylation, was not persistently more prevalent in CIMP-low tumors. In conclusion, compared to CIMP-high and CIMP-0 tumors, CIMP-low colorectal cancers show not only few methylated CIMP-high-specific CpG islands, but also more frequent low-level methylation at individual loci. Our data may provide supporting evidence for a difference in pathogenesis of DNA methylation between CIMP-low and CIMP-high tumors.

Published
2008
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2. WRN promoter methylation possibly connects mucinous differentiation, microsatellite instability and CpG island methylator phenotype in colorectal cancer.

Author

Kawasaki T, Ohnishi M, Suemoto Y, Kirkner GJ, Liu Z, Yamamoto H, Loda M, Fuchs CS, and Ogino S

Subjects
Adenocarcinoma, Mucinous metabolism, Adenocarcinoma, Mucinous pathology, Cell Transformation, Neoplastic, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Databases, Genetic, Exodeoxyribonucleases metabolism, Female, Gene Expression Regulation, Neoplastic, Gene Silencing, Humans, Loss of Heterozygosity genetics, Male, Microsatellite Instability, Phenotype, Prospective Studies, RecQ Helicases metabolism, Werner Syndrome Helicase, Adenocarcinoma, Mucinous genetics, Colorectal Neoplasms genetics, CpG Islands genetics, DNA Methylation, Exodeoxyribonucleases genetics, Mucins metabolism, RecQ Helicases genetics
Abstract

Werner syndrome is a premature aging syndrome characterized by early onset of cancer and abnormal cellular metabolism of glycosaminoglycan. The WRN helicase plays an important role in the maintenance of telomere function. WRN promoter methylation and gene silencing are common in colorectal cancer with the CpG island methylator phenotype (CIMP), which is associated with microsatellite instability (MSI) and mucinous tumors. However, no study has examined the relationship between mucinous differentiation, WRN methylation, CIMP and MSI in colorectal cancer. Utilizing 903 population-based colorectal cancers and real-time PCR (MethyLight), we quantified DNA methylation in WRN and eight other promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) known to be specific for CIMP. Supporting WRN as a good CIMP marker, WRN methylation was correlated well with CIMP-high diagnosis (> or =6/8 methylated promoters), demonstrating 89% sensitivity and 81% specificity. WRN methylation was associated with the presence of any mucinous component and > or =50% mucinous component (P<0.0001). Because both MSI and CIMP were associated with mucinous tumors and WRN methylation, we stratified tumors into 9 MSI/CIMP subtypes, to examine whether the relationship between WRN methylation and mucin still persisted. In each MSI/CIMP subtype, tumors with mucinous component were persistently more common in WRN-methylated tumors than WRN-unmethylated tumors (P=0.004). No relations of WRN methylation with other variables (age, sex, tumor location, poor differentiation, signet ring cells, lymphocytic reactions, KRAS, BRAF, p53, p21 or 18q loss of heterozygosity) persisted after tumors were stratified by CIMP status. In conclusion, WRN methylation is associated with mucinous differentiation independent of CIMP and MSI status. Our data suggest a possible role of WRN methylation in mucinous differentiation, and may provide explanation to the enigmatic association between mucin and MSI/CIMP.

Published
2008
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