Streamlining Detection of Fusion Genes in Colorectal Cancer: Having "Faith" in Precision Oncology in the (Tissue) "Agnostic" Era.

Abstract

The FDA recently granted tissue-agnostic approval for the first-in-class TRK inhibitor larotrectinib for patients whose tumors harbor fusions in neurotrophic receptor tyrosine kinases. These fusion genes have a frequency of less than 1% in unselected patients with colorectal cancer. Using a multiomics approach and a clinically annotated cohort of patients with colorectal cancer, Cocco and colleagues showed that patients with sporadic, <i>RAS</i>/<i>BRAF</i> wild-type, mismatch repair-deficient colorectal cancer tumors with MLH1 promoter methylation present fusions in kinase genes in 42% of cases and suggested a diagnostic framework to improve the selection of patients eligible for gene fusion testing.<i>See related article by Cocco et al., p. 1047</i>.