Identification of highly penetrant Rb-related synthetic lethal interactions in triple negative breast cancer.

ABSTRACT: Although defects in the RB1 tumour suppressor are one of the more common driver alterations found in triple-negative breast cancer (TNBC), therapeutic approaches that exploit this have not been identified. By integrating molecular profiling data with data from multiple genetic perturbation screens, we identified candidate synthetic lethal (SL) interactions associated with RB1 defects in TNBC. We refined this analysis by identifying the highly penetrant effects, reasoning that these would be more robust in the face of molecular heterogeneity and would represent more promising therapeutic targets. A significant proportion of the highly penetrant RB1 SL effects involved proteins closely associated with RB1 function, suggesting that this might be a defining characteristic. These included nucle

SUBMITTER: Brough R 

PROVIDER: S-EPMC6202330 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature