BRAF Mutation and Microsatellite Instability Status in Colonic and Rectal Carcinoma : Context Really Does Matter
Menée sur 1 253 patients atteints d'un cancer du côlon ou du rectum et inclus dans deux études de cohorte comportant des professionnels de santé, cette étude évalue, du point de vue de la survie, la valeur pronostique de la présence d'une mutation du gène BRAF en fonction du statut des microsatellites (stable ou instable)
The molecular characteristics of colorectal cancer (CRC) have been studied extensively since the 1980s, but translation of the remarkable increase in genomic knowledge into clinically used biomarkers has been distressingly slow. The Cancer Genome Atlas for CRC was published in mid-2012 (1), and molecular and pathologic findings including genetic and epigenetic abnormalities have now been incorporated into classification systems that have been reported to have implications for the clinical management of patients (2–4). Numerous individual molecular biomarkers with potential applications have been published, but few have achieved levels and breadth of evidence to become standard of care. Difficulty in convincing payers of the value of biomarkers and fiscal constraints have impeded adequate reimbursement for testing and disincentivized their clinical use.
In this issue of the Journal, Lochhead and colleagues (5) provide important additional evidence supporting the routine clinical use in CRC patients of two extensively investigated molecular alterations: microsatellite instability and BRAF mutation. Both of these characteristics of CRC are in use as biomarkers (6), but they have been uncommonly addressed together in the four microsatellite instability (MSI)/BRAF subgroups for clinical usage in prognostication.
High levels of MSI (MSI-H) occur in about 15% of CRC, and the presence of this feature is a hallmark of Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). Although most MSI-H CRC are sporadic because of acquired hypermethylation of the MLH1 mismatch repair gene promoter region, germline mutation in one of several mismatch repair genes, most frequently MLH1 or MSH2, results in MSI-H tumors in Lynch syndrome patients. At least three professional organizations (7–9) have issued recommendations for routine testing for MSI status in CRC to identify tumors in patients…
Journal of the National Cancer Institute , éditorial, 2013