【摘 要】
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Background & Aims: DNA methylation is essential for normal development and is frequently altered in cancers.CpG Island Methylator Phenotype (CIMP) is a subset of colorectal cancers was postulated to h
【机 构】
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Department of medical genetics, Second Military Medical University, Shanghai, 200433
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Background & Aims: DNA methylation is essential for normal development and is frequently altered in cancers.CpG Island Methylator Phenotype (CIMP) is a subset of colorectal cancers was postulated to have a higher propensity for DNA methylation.However, the validity of CIMP, its molecular basis, and its prognostic values are highly controversial.The aims of this study were to (1) compare and characterize the unique features of DNA methylomes of CIMP with Non-CIMP colonrectal cancers; (2) propose a new panel of valuable markers for CIMP screening.Methods & Results: Here we utilized MBD-isolated Genome Sequencing (MiGS) to map the DNA methylomes of three sets of normal colon, non-CIMP colon cancers, and CIMP colon cancers.Some regions only robust hypermethylated in CIMP tumors were evaluated in 120 colorectal tumors by Bisulfite genomic sequencing or Methylation Specific PCR (MSP).We found 4,800 sites were hypermnethylated in both non-CIMP and CIMP colon cancers when compared with normal colon.Of those sites, 318 sites were robust hypermethylated in CIMP tumors only.Methylation of these CpG islands regulates 122 key genes in tumorgenesis and progress.A panel of 5 new markers was proposed for CIMP screening in 120 consecutive colon samples, 13.3% (16/120) were methylated in all 5 markers and 87.5% (14/16) were MSI.Using the markers described by Weisenberger et al., 22.5% (27/120) were methylated in all 5 markers and only 51.8% (14/27) were MSI cancers.Conclusions: CIMP are a subset ofcolorectal cancer has unique features in DNA Methylomes.The genes only hypermethylated in CIMP tumors shed lights on exploration the mechanism of CIMP tumorgenesis and provide new targets for cancer therapies.The new panel of markers facilitates CIMP screening in sporadic colorectal cancers.
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