Identification of phenocopies improves prediction of targeted therapy response over DNA mutations alone.

ABSTRACT: DNA mutations in specific genes can confer preferential benefit from drugs targeting those genes. However, other molecular perturbations can "phenocopy" pathogenic mutations, but would not be identified using standard clinical sequencing, leading to missed opportunities for other patients to benefit from targeted treatments. We hypothesized that RNA phenocopy signatures of key cancer driver gene mutations could improve our ability to predict response to targeted therapies, despite not being directly trained on drug response. To test this, we built gene expression signatures in tissue samples for specific mutations and found that phenocopy signatures broadly increased accuracy of drug response predictions in-vitro compared to DNA mutation alone, and identified additional cancer cell lines t

SUBMITTER: Bakhtiar H 

PROVIDER: S-EPMC9576758 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature