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Related Experiment Video

Updated: Feb 1, 2026

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

BRCA1/2 Functional Loss Defines a Targetable Subset in Leiomyosarcoma.

Nathan D Seligson^1,2, Esko A Kautto³, Edward N Passen⁴

¹Division of Pharmacy Practice and Science, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.

|December 14, 2018

Summary

Uterine leiomyosarcoma (uLMS) shows a higher frequency of BRCA2 alterations. Patients with uLMS and BRCA2 loss may benefit from PARP inhibitors, warranting further investigation.

Keywords:

DNA repair Homologous recombination Poly (ADP‐ribose) polymerase inhibitors Sarcoma

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Published on: February 26, 2019

Area of Science:

Oncology
Genetics
Molecular Biology

Background:

Soft-tissue sarcomas (STS) are a diverse group of mesenchymal tumors with limited therapeutic options.
The prevalence and clinical significance of homologous recombination (HR) DNA repair pathway alterations, including BRCA1/2, in STS subtypes require further elucidation.
This study aims to characterize HR pathway alterations across various STS subtypes, with a focus on leiomyosarcoma (LMS).

Observation:

Analysis of 1,236 STS patient samples revealed BRCA2 alterations in 15 (1%) and homozygous BRCA2 loss in 9 (<1%) patients.
Subset analysis demonstrated that BRCA2 alterations were significantly concentrated in uterine LMS (uLMS), occurring in 10% of uLMS tumors.
Four uLMS patients with BRCA2 loss exhibited a durable clinical response to poly (ADP-ribose) polymerase (PARP) inhibition.

Findings:

Homologous recombination pathway alterations are infrequent in the general STS population.
Uterine LMS is uniquely enriched for BRCA2 loss compared to other STS subtypes.
PARP inhibitors demonstrated clinical efficacy in a small cohort of uLMS patients with BRCA2 loss.

Implications:

Patients with uLMS should be considered for somatic BRCA2 profiling due to the increased prevalence of these alterations.
The findings suggest that uLMS patients with BRCA2 loss may benefit from targeted therapy with PARP inhibitors.
Prospective clinical trials are essential to validate the efficacy of PARP inhibition in uLMS and establish its role in treatment strategies.