Microsatellite Instability and BRAF Mutation Testing in Colorectal Cancer Prognostication
2013/07/22 by Paul Lochhead, Aya Kuchiba, Yu Imamura +9 · 447 citations
Medicine · #Allele #Biology #Cancer #Cancer research #Colorectal Cancer Screening and Detection #Colorectal Cancer Treatments and Studies #Colorectal cancer #Confidence interval #DNA mismatch repair #Gene #Genetic factors in colorectal cancer #Genetics #Hazard ratio #Internal medicine #KRAS #MLH1 #Medicine #Microsatellite #Microsatellite instability #Oncology
paper · pdf · doi:10.1093/jnci/djt173
published in JNCI Journal of the National Cancer Institute 105(15), 1151-1156 (Oxford University Press)
openalex publication_date 2013/07/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
Abstract
BRAF mutation in colorectal cancer is associated with microsatellite instability (MSI) through its relationship with high-level CpG island methylator phenotype (CIMP) and MLH1 promoter methylation. MSI and BRAF mutation analyses are routinely used for familial cancer risk assessment. To clarify clinical outcome associations of combined MSI/BRAF subgroups, we investigated survival in 1253 rectal and colon cancer patients within the Nurses' Health Study and Health Professionals Follow-up Study with available data on clinical and other molecular features, including CIMP, LINE-1 hypomethylation, and KRAS and PIK3CA mutations. Compared with the majority subtype of microsatellite stable (MSS)/BRAF-wild-type, MSS/BRAF-mutant, MSI-high/BRAF-mutant, and MSI-high/BRAF-wild-type subtypes showed multivariable colorectal cancer-specific mortality hazard ratios of 1.60 (95% confidence interval [CI] =1.12 to 2.28; P = .009), 0.48 (95% CI = 0.27 to 0.87; P = .02), and 0.25 (95% CI = 0.12 to 0.52; P < .001), respectively. No evidence existed for a differential prognostic role of BRAF mutation by MSI status (P(interaction) > .50). Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification.
Citations
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- Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. [europepmc]
- Association between molecular subtypes of colorectal cancer and patient survival. [europepmc]
- Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma. [europepmc]
- The microsatellite instable subset of colorectal cancer is a particularly good candidate for checkpoint blockade immunotherapy. [europepmc]
- High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort. [europepmc]
- Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers. [europepmc]
- Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. [europepmc]
- BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict Responsiveness to BRAF-MEK Combination Therapy. [europepmc]
- Colorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients. [europepmc]
- Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology. [europepmc]
- Maturation of tertiary lymphoid structures and recurrence of stage II and III colorectal cancer. [europepmc]
- Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAF V600E -Mutant Colorectal Cancer. [europepmc]
- Are Colon and Rectal Cancer Two Different Tumor Entities? A Proposal to Abandon the Term Colorectal Cancer. [europepmc]
- Intertumoral Heterogeneity of CD3 + and CD8 + T-Cell Densities in the Microenvironment of DNA Mismatch-Repair-Deficient Colon Cancers: Implications for Prognosis. [europepmc]
- Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E-Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study. [europepmc]
- Comprehensive Genomic Landscapes in Early and Later Onset Colorectal Cancer. [europepmc]
- Biomarker-guided therapy for colorectal cancer: strength in complexity. [europepmc]
- Applications and analysis of targeted genomic sequencing in cancer studies. [europepmc]
- Novel biomarkers for the diagnosis and prognosis of colorectal cancer. [europepmc]
- The heterogeneous clinical and pathological landscapes of metastatic Braf -mutated colorectal cancer. [europepmc]
- Clinical-Grade Detection of Microsatellite Instability in Colorectal Tumors by Deep Learning. [europepmc]
- Epigenetic Alterations in the Gastrointestinal Tract: Current and Emerging Use for Biomarkers of Cancer. [europepmc]
- Novel Genetic and Epigenetic Biomarkers of Prognostic and Predictive Significance in Stage II/III Colorectal Cancer. [europepmc]
- Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population. [europepmc]
- Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis. [europepmc]
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