Rational testing for gene fusion in colorectal cancer: MSI and RAS-BRAF wild-type metastatic colorectal cancer as target population for systematic screening

Gene fusions provide access to new therapeutic opportunities for patients treated for a colorectal cancer (CRC). However, they do not excess 1% of patients. A better identification of patients in whom gene fusions are highly prevalent is a major issue in a therapeutic and medico-economics perspective. This study assesses the rates of gene fusions in CRC patients with MSI/RAS-BRAF (c) in our routine practice detected with a commercially available NGS-based fusion panel. Among the 130 MSI CRC tumors, 43 (33%) were KRASNRAS-BRAF(WT). A gene fusion was detected in 7 ( 25.9%) of the 27 MSI/RAS-BRAF(WT) samples, which had RNA suitable for analysis after quality control. These fusions involved mainly NTRK1/3 (n = 5), as well as ALK (n = 1) and BRAF (n = 1). In the present study, we confirm that patients with MSI/RAS-BRAF(WT) CRCs represent a subpopulation in which targetable gene fusions are overrepresented. Our results support the use of a two-step algorithm for molecular screening, in which metastatic CRC patients would have routine MSI and RAS/BRAF testing, and then only those with MSI/RAS-BRAF(WT) would be screened with dedicated NGS RNA panel for gene fusions. (C) 2022 Elsevier Ltd. All rights reserved.