Concomitant mutations and splice variants in <i>KRAS</i> and <i>BRAF</i> demonstrate complex perturbation of the Ras/Raf signalling pathway in advanced colorectal cancer

Disrupted Ras/Raf signalling is common in CRC. Homozygous KRAS mutations and concomitant KRAS/BRAF mutations may be indicative of a gene dosage effect. The significance of BRAF splice variants is uncertain but may represent another layer of complexity. Finally, if KRAS mutation is to be used for predictive testing, then the whole gene may need to be screened as mutations occur outside codons 12/13.