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However, except for these specific HR genes, it is not clear which other mutations contribute to homologous recombination defects (HRD). Here, we performed next\u2010generation sequencing of tumor tissues and matched blood samples from 119 breast cancer patients using the OncoScreen Plus panel. Genomic mutation characteristics and HRD scores were analyzed. In the HR genes, we found that <jats:italic>BRCA1\/2<\/jats:italic> and <jats:italic>PLAB2<\/jats:italic> mutations were related to HRD. HRD was also detected in a subset of patients without germline or somatic mutations in <jats:italic>BRCA1\/2<\/jats:italic>, <jats:italic>PLAB2<\/jats:italic>, or other HR\u2010related genes. Notably, <jats:italic>LRP1B<\/jats:italic>, <jats:italic>NOTCH3<\/jats:italic>, <jats:italic>GATA2<\/jats:italic>, and <jats:italic>CARD11<\/jats:italic> (abbreviated as LNGC) mutations were associated with high HRD scores in breast cancer patients. Furthermore, functional experiments demonstrated that silencing CARD11 and GATA2 impairs HR repair efficiency and enhances the sensitivity of tumor cells to olaparib treatment. In summary, in the absence of mutations in the HR genes, the sensitivity of tumor cells to PARP inhibitors and platinum\u2010based chemotherapy may be enhanced in a subset of breast cancer patients with LNGC somatic mutations.<\/jats:p>","DOI":"10.1002\/2056-4538.12367","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T00:34:46Z","timestamp":1710894886000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Somatic mutations in four novel genes contribute to homologous recombination deficiency in breast cancer: a real\u2010world clinical tumor sequencing study"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8449-7522","authenticated-orcid":false,"given":"Yongsheng","family":"Huang","sequence":"first","affiliation":[{"name":"Cellular &amp; Molecular Diagnostics Center Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010sen University  Guangzhou PR 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