BRCA1/2 Functional Loss Defines a Targetable Subset in Leiomyosarcoma

AbstractBackground.Soft‐tissue sarcomas (STS) describe a heterogeneous group of mesenchymal tumors with limited treatment options. Targeted therapies exist for BRCA1/2 gene alterations, but their prevalence and role have not been fully described in STS. Here, we present the largest effort to characterize the frequency of homologous recombination (HR) DNA repair pathway alterations in STS subtypes and highlight the unique nature of leiomyosarcoma (LMS).Materials and Methods.DNA sequencing data were analyzed for HR pathway alterations for 1,236 patients with STS. DNA sequencing data from an additional 1,312 patients were used to confirm the prevalence of HR pathway alterations in LMS. Four uterine LMS (uLMS) patients with functional BRCA2 loss were evaluated for response to poly (ADP‐ribose) polymerase (PARP) inhibition.Results.In an unselected STS study population, BRCA2 alterations were identified in 15 (1%) patients, and homozygous BRCA2 loss was detected in 9 (

Source: The Oncologist - July 16, 2019 Category: Cancer & Oncology Authors: Nathan D. Seligson, Esko A. Kautto, Edward N. Passen, Colin Stets, Amanda E. Toland, Sherri Z. Millis, Christian F. Meyer, John L. Hays, James L. Chen Tags: Sarcomas, Precision Medicine Clinic: Molecular Tumor Board Source Type: research