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Evaluation of Markers for CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer by a Large Population-Based Sample  Shuji Ogino, Takako Kawasaki,

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Presentation on theme: "Evaluation of Markers for CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer by a Large Population-Based Sample  Shuji Ogino, Takako Kawasaki,"— Presentation transcript:

1 Evaluation of Markers for CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer by a Large Population-Based Sample  Shuji Ogino, Takako Kawasaki, Gregory J. Kirkner, Peter Kraft, Massimo Loda, Charles S. Fuchs  The Journal of Molecular Diagnostics  Volume 9, Issue 3, Pages (July 2007) DOI: /jmoldx Copyright © 2007 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

2 Figure 1 BRAF and KRAS mutation frequencies according to number of methylated promoters. A: Tumors with ≥6/8 methylated promoters show high BRAF mutation rates, whereas tumors with ≤5/8 methylated promoters show high KRAS mutation rates. B: MSI-H tumors distribute bimodally, and the frequencies of KRAS and BRAF mutations clearly distinguish CIMP-high tumors from CIMP-low tumors. C: MSI-L/MSS tumors can be separated into CIMP-high (≥6/8 methylated promoters) and CIMP-low/0 (≤4/8 methylated promoters) based on the frequencies of BRAF and KRAS mutations. Tumors with 5/8 methylated promoters reside on the borderline between CIMP-high and CIMP-low. The Journal of Molecular Diagnostics 2007 9, DOI: ( /jmoldx ) Copyright © 2007 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

3 Figure 2 Sensitivity, specificity, and cross-panel classification error rate against panel 8. Panel 1 (RUNX3 only) through panel 7 contain incrementing numbers of markers, adding one by one from CACNA1G, IGF2, MLH1, NEUROG1, CRABP1, and SOCS1. Panel 8 contains all eight markers including CDKN2A. A: Specificity generally increases with an increasing number of markers. Sensitivity depends on the number of markers and a CIMP-high cutoff. B: The classification error rate decreases with an increasing number of markers. The Journal of Molecular Diagnostics 2007 9, DOI: ( /jmoldx ) Copyright © 2007 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

4 Figure 3 Frequencies of right-sided tumors (A), poorly differentiated tumors (B), and mucinous tumors (C) in various MSI/CIMP subtypes of colorectal cancer. Gray and open bar graphs indicate frequencies of each feature in MSI/CIMP subtypes determined by CIMP panel 4 and CIMP panel 8, respectively. Note that there were no substantial differences in the features examined (anatomical location, tumor grade, or mucinous features) between classifications determined by CIMP panel 4 and panel 8. The Journal of Molecular Diagnostics 2007 9, DOI: ( /jmoldx ) Copyright © 2007 American Society for Investigative Pathology and Association for Molecular Pathology Terms and Conditions

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