(ChemotherapyAdvisor) – Investigators have derived a high-sensitivity gene expression signature for BRAF-mutant colon cancer that also identified a population of BRAF mutation-like KRAS mutants and double wild-type patients with similarly poor prognosis, according to a study in the Journal of Clinical Oncology published online March 5.
These findings “challenge the current assumption that these tumors can all be considered alike,” the investigators wrote. For example, genes associated with the colon-cancer mutation are dissimilar to those in melanoma, “indicating tissue-specific biology that needs to be understood and targeted differently. It is therefore not surprising that BRAF-specific inhibitors, such as PLX4032 or GSK2118436, although very successful in BRAF-mutant melanoma, have failed in BRAF-mutant colorectal-cancer treatment.”
A set of 668 stage II and III colon-cancer samples from the Pan-European Trials in Alimentary Tract Cancers (PETACC-3) was used to assess differential gene expression. The 64 gene-based classifier developed had 96% sensitivity and 86% specificity for detecting BRAF mutant tumors in PETACC-3 and independent samples.
A subpopulation of BRAF wild-type patients — 30% of KRAS mutants and 13% of double wild type — had a gene expression pattern linked to poor overall survival and survival after relapse. These results were similar to those observed in BRAF-mutant patients and formed a distinct prognostic subgroup within their mutation class.