CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer
By S. Ogino, K. Nosho, G. Kirkner, Takako Kawasaki, J. Meyerhardt, M. Loda, Edward L. Giovannucci, C. Fuchs. Gut, 2008
810 citations recorded by the source corpus.
Background: The CpG island methylator phenotype (CIMP), characterised by widespread promoter methylation, is associated with microsatellite instability (MSI) and BRAF mutation in colorectal cancer. The independent effect of CIMP, MSI and BRAF mutation on prognosis remains uncertain. Methods: Utilising 649 colon cancers (stage I–IV) in two independent cohort studies, we quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) as well as CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, and WRN by using MethyLight technology. We examined MSI, KRAS and BRAF status. Cox proportional hazard models computed hazard ratios (HRs) for colon cancer-specific and overall mortalities, adjusting for patient characteristics and tumoral molecular features. Results: After adjustment for other predictors of patient survival, patients with CIMP-high cancers (126 (19%) tumours with ⩾6/8 methylated CIMP-specific promoters) experienced a significantly low colon cancer-specific mortality (multivariate HR 0.44, 95% confidence interval (CI) 0.22 to 0.88), whereas the BRAF mutation was significantly associated with a high cancer-specific mortality (multivariate HR 1.97, 95% CI 1.13 to 3.42). A trend toward a low cancer-specific mortality was observed for MSI-high tumours (multivariate HR 0.70, 95% CI 0.36 to 1.37). In stratified analyses, CIMP-high tumours were associated with a significant reduction in colon cancer-specific mortality, regardless of both MSI and BRAF status. The relation between CIMP-high and lower mortality appeared to be consistent across all stages. KRAS mutation was unrelated to prognostic significance. Conclusion: CIMP-high appears to be an independent predictor of a low colon cancer-specific mortality, while BRAF mutation is associated with a high colon cancer-specific mortality.
Subfields: Molecular Biology, Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/65484db3814ab6da7ae85f7f5e3c827c288b1100
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Citations in the corpus
- Impact of BRAF Mutation and Microsatellite Instability on the Pattern of Metastatic Spread and Prognosis in Metastatic Colorectal Cancer (2011, background): “In the metastatic setting, the majority of patients have epigenetic loss as the mechanism of MSI, which is associated with BRAFmutations.(19) Indeed, in our population, BRAF mutant tumors are more prevalent in the MSI population (29%) than the Original Article”
- Aspirin Use, Tumor PIK3CA Mutation, and Colorectal-Cancer Survival (2012, neutral): “I 260 (27) 112 (24) 102 (30) 19 (20) 27 (41)”
- Fusobacterium nucleatum and T-cells in Colorectal Carcinoma (2015, neutral): “0001 High 94 (16) 66 (13) 12 (33) 16 (42)”
- Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer (2017, background): “In addition to this, BRAF mutations also have a poor prognosis associated with lower survival rates, especially in those tumours with microsatellite instability [38–40].”
- Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours (2013, background): “CIMP-high might be a prognostic marker independent of the presence of MSI and BRAF mutation [17].”