Published in:
01-09-2014 | Adjuvant Therapy for Colon Cancers (AB Benson III and A de Gramont, Section Editors)
Prognostic Impact of Deficient DNA Mismatch Repair and KRAS and BRAF
V600E Mutations in Patients with Lymph-Node-Positive Colon Cancer
Authors:
Aziz Zaanan, Jean-Baptiste Bachet, Thierry André, Frank A. Sinicrope
Published in:
Current Colorectal Cancer Reports
|
Issue 3/2014
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Abstract
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.