Clinical–Alimentary Tractp14 methylation in human colon cancer is associated with microsatellite instability and wild-type p53☆,☆☆
Section snippets
Tissue samples and cell lines
Tumor samples and corresponding adjacent tissues were collected from consenting patients in accordance with institutional policies, flash frozen, and stored at −70°C in a tumor bank. We have reported previously 3, 6, 17 on 100 colon cancers studied for the presence of CIMP, MSI (determined according to strict criteria, testing at least 5 markers, and requiring band shifts at both dinucleotide and mononucleotide tracts), p16 methylation, K-RAS codon 12 and 13 mutations (determined by the
A quantitative p14 methylation assay
Methylation assays vary in their sensitivity, which sometimes affects reproducibility of results. Bisulfite conversion coupled with PCR and restriction fragment length polymorphism (COBRA) is a robust quantitative assay that usually requires substantial methylation for detection in primary tissues, and therefore is associated strongly with gene silencing. We used a set of primers to amplify the 5' region of the p14 promoter and coupled these with restriction enzymes that digest only methylated
Discussion
Our results clearly show an inverse relationship between p14 methylation and p53 mutations in sporadic colorectal cancer, and provide additional support for the hypothesis that p14 inactivation is equivalent functionally to p53 mutations in abrogating the p53 pathway.12, 13 These results, along with the high frequency of p14 methylation in sporadic colorectal cancers with MSI-H provide an attractive explanation for the puzzling lack of p53 mutations in MSI-H cases. Thus, given that most
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Theories of stem cell aging
2021, Stem Cells and AgingClinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis
2018, Translational OncologyCitation Excerpt :While CIMP-H patients were older at diagnosis compare to CIMP-0 patients (P < .001), the magnitude of this difference was modest (standardized mean difference = 0.89 years, 95% CI = 0.28-1.50 years), confirming previous association of CIMP-H with older age. We also studied the association of CIMP with race/ethnicity across four studies [32–35]. Using non-Hispanic whites as a reference group, we identified that patients of black race had substantially lower likelihood of having a CIMP-H tumor (pooled OR = 0.35, 95% CI = 0.21-0.56).
Aberrant DNA Methylation in Colorectal Cancer: What Should We Target?
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Supported by research grants from the American Cancer Society (RPG9909801MGO), the National Cancer Institute (R01 CA89245-01), the George and Barbara Bush fund for innovative cancer research, and the Yasuda Medical Research Foundation and the Nitto foundation in Japan (to Y.K.). DNA sequencing in the MDACC core sequencing facility was supported by core grant CA16672 from the National Institutes of Health.
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Address requests for reprints to: Jean-Pierre Issa, M.D., Department of Leukemia, MD Anderson Cancer Center, Box 428, 1515 Holcombe, Houston, Texas 77030. e-mail: [email protected]; fax: (713) 794-4297.