Prognostic Impact of Deficient DNA Mismatch Repair and KRAS and BRAF V600E Mutations in Patients with Lymph-Node-Positive Colon Cancer
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Although tumor stage remains the key determinant of colorectal cancer prognosis and treatment, there is considerable stage-independent variability in clinical outcome. Molecular markers hold promise for explaining variations in clinical behavior, and may identify patient subsets with differential efficacy and survival after adjuvant chemotherapy, which is the standard of care for patients with lymph-node-positive, i.e., stage III, colon cancer. An increased understanding of the molecular evolution and progression of colorectal cancer has identified two major pathways of tumorigenesis that are characterized by chromosomal instability and by microsatellite instability. Microsatellite instability is a consequence of deficient DNA mismatch repair that is generally due to epigenetic inactivation of MLH1 in tumors that often carry mutations (V600E) in oncogenic BRAF. Activating BRAF V600E and KRAS mutations are mutually exclusive, and in this article, we review the current status of these mutations and the mismatch repair status as prognostic biomarkers in stage III colon cancers.
KeywordsColorectal cancer Microsatellite instability BRAF KRAS Biomarker Prognosis
This work was supported, in part, by the French National Institute for Health and Medical Research (INSERM) (to Aziz Zaanan) and by a Senior Scientist Award (K05CA-142885 to Frank A. Sinicrope ) from the US National Cancer Institute.
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Conflict of Interest
Aziz Zaanan and Thierry André declare that they have no conflict of interest.
Jean-Baptiste Bachet has received support through grants from Amgen and Celgene, and has received compensation from Amgen, Merck Serono, Roche, Sanofi-Aventis, Novartis, and Lilly for service as a consultant.
Frank A. Sinicrope has received support through grants from the National Institutes of Health, Sanofi-Aventis, Imclone, Bristol-Myers Squibb, and Pfizer.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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