Molecular Pathways : microsatellite instability in colorectal cancer: prognostic, predictive and therapeutic implications
Cet article passe en revue les perspectives offertes par les travaux récents sur l'instabilité microsatellitaire pour développer des biomarqueurs dans le cancer colorectal
Microsatellite instability (MSI) is the molecular fingerprint of the deficient mismatch repair (MMR) system that characterizes approximately 15% of colorectal cancers (CRCs). MSI develops due to germline mutations in MMR genes or more commonly, from epigenetic silencing of MLH1 in sporadic tumors that occurs in a background of methylation of CpG islands in gene promoter regions and in tumors that frequently show hotspot mutations in the BRAF oncogene. MSI tumors have distinct phenotypic features and have been consistently associated with a better stage-adjusted prognosis compared to microsatellite stable tumors. MSI negatively predicts response to 5-fluorouracil and may also determine responsiveness to other drugs used in CRC treatment. Recent data expand the molecular heterogeneity of MSI tumors that may contribute to the understanding of differential chemosensitivity. Identifying deficient MMR has important implications for patient management and its exploitation holds promise for improving patient outcomes and for the development of novel therapeutics.
Clinical Cancer Research , résumé, 2012