Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma.

ABSTRACT: Defects in homologous recombination repair (HRR) in tumors correlate with poor prognosis and metastases development. Determining HRR deficiency (HRD) is of major clinical relevance as it is associated with therapeutic vulnerabilities and remains poorly investigated in sarcoma. Here, we show that specific sarcoma entities exhibit high levels of genomic instability signatures and molecular alterations in HRR genes, while harboring a complex pattern of chromosomal instability. Furthermore, sarcomas carrying HRDness traits exhibit a distinct SARC-HRD transcriptional signature that predicts PARP inhibitor sensitivity in patient-derived sarcoma cells. Concomitantly, HRD^high sarcoma cells lack RAD51 nuclear foci formation upon DNA damage, further evidencing defects in HRR. We further i

SUBMITTER: Planas-Paz L 

PROVIDER: S-EPMC10086583 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature