BRCA1/2 Functional Loss Defines a Targetable Subset in Leiomyosarcoma

Autor: Sherri Z. Millis, Amanda E. Toland, John L. Hays, Christian F. Meyer, James L. Chen, Nathan D. Seligson, Esko A. Kautto, Colin W. Stets, Edward N. Passen
Rok vydání: 2018
Předmět:
Zdroj: The Oncologist. 24:973-979
ISSN: 1549-490X
1083-7159
Popis: Background 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 ( Conclusion HR pathway alterations are rare in most STS. However, we identify uLMS to be enriched for BRCA2 loss and report the positive outcomes of a series of patients treated with PARP inhibitors. Our data suggest that patients with uLMS should be considered for somatic BRCA2 profiling. Prospective trials are necessary to confirm the efficacy of PARP inhibition in uLMS.
Databáze: OpenAIRE
Externí odkaz: