Microsatellite Instability and BRAF Mutation Testing in Colorectal Cancer Prognostication
Top Cited Papers
Open Access
- 22 July 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in JNCI Journal of the National Cancer Institute
- Vol. 105 (15), 1151-1156
- https://doi.org/10.1093/jnci/djt173
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 (Pinteraction > .50). Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification.This publication has 81 references indexed in Scilit:
- Aspirin Use, TumorPIK3CAMutation, and Colorectal-Cancer SurvivalNew England Journal of Medicine, 2012
- Whole‐genome methylation analysis of benign and malignant colorectal tumoursThe Journal of Pathology, 2012
- The CpG island methylator phenotype in colorectal cancer: Progress and problemsBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2012
- Epigenetics and colorectal cancerNature Reviews Gastroenterology & Hepatology, 2011
- Cancer immunology—analysis of host and tumor factors for personalized medicineNature Reviews Clinical Oncology, 2011
- Association of CTNNB1 (β-Catenin) Alterations, Body Mass Index, and Physical Activity With Survival in Patients With Colorectal CancerJAMA, 2011
- BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancerBritish Journal of Cancer, 2011
- Tumour‐infiltrating T‐cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature reviewThe Journal of Pathology, 2010
- Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancerBritish Journal of Cancer, 2009
- CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancerNature Genetics, 2006