Unravelling HRDness and therapeutic opportunities in soft tissue and bone sarcoma

ABSTRACT: Defects in homologous recombination repair (HRR) in tumours 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 harbouring 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, HRDhigh sarcoma cells lack RAD51 nuclear foci formation upon DNA damage, further evidencing defects in HRR. We further identify t

SUBMITTER: Dr. Lara Planas-Paz 

PROVIDER: S-SCDT-10_15252-EMMM_202216863 | biostudies-other |

REPOSITORIES: biostudies-other