Novel fusions impacting CRC-relevant pathways inactivated APC or SMAD4, or were activating fusions such as a TRIM24-BRAF (in 196_T MSI) (Fig. 2a) predicted to trigger the conformational activation of the BRAF serine/threonine kinase domain, as observed in pilocytic astrocytoma19 and melanoma20. This evidence concerns the gene SMAD4 and colorectal carcinoma.