{"doi":"10.1158/1078-0432.c.6532794","title":"Data from Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers","abstract":"<div>AbstractPurpose:<p>The identification of patients with homologous recombination deficiency (HRD) beyond <i>BRCA1/2</i> mutations is an urgent task, as they may benefit from PARP inhibitors. We have previously developed a method to detect mutational signature 3 (Sig3), termed SigMA, associated with HRD from clinical panel sequencing data, that is able to reliably detect HRD from the limited sequencing data derived from gene-focused panel sequencing.</p>Experimental Design:<p>We apply this method to patients from two independent datasets: (i) high-grade serous ovarian cancer and triple-negative breast cancer (TNBC) from a phase Ib trial of the PARP inhibitor olaparib in combination with the PI3K inhibitor buparlisib (BKM120; NCT01623349), and (ii) TNBC patients who received neoadjuvant olaparib in the phase II PETREMAC trial (NCT02624973).</p>Results:<p>We find that Sig3 as detected by SigMA is positively associated with improved progression-free survival and objective responses. In addition, comparison of Sig3 detection in panel and exome-sequencing data from the same patient samples demonstrated highly concordant results and superior performance in comparison with the genomic instability score.</p>Conclusions:<p>Our analyses demonstrate that HRD can be detected reliably from panel-sequencing data that are obtained as part of routine clinical care, and that this approach can identify patients beyond those with germline <i>BRCA1</i>/<i>2</i>mut who might benefit from PARP inhibitors. Prospective clinical utility testing is warranted.</p></div>","journal":null,"year":2023,"id":405707,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":556245,"name":"D. Gulhan","orcid":"0000-0001-5419-0549","position":1,"is_corresponding":false},{"id":1087649,"name":"Victor Y. Mao","orcid":"0000-0001-5051-2459","position":2,"is_corresponding":false},{"id":859537,"name":"Antuan V. Tran","orcid":"0000-0002-3911-1686","position":3,"is_corresponding":false},{"id":650976,"name":"Madeline Polak","orcid":"0000-0002-1331-3845","position":4,"is_corresponding":false},{"id":717898,"name":"Niya Xiong","orcid":"0000-0003-2496-9409","position":5,"is_corresponding":false},{"id":352704,"name":"Nabihah Tayob","orcid":"0000-0001-6088-167X","position":6,"is_corresponding":false},{"id":333640,"name":"Nadine Tung","orcid":"0000-0003-1422-3734","position":7,"is_corresponding":false},{"id":3752,"name":"Eric P. Winer","orcid":"0000-0002-8819-1723","position":8,"is_corresponding":false},{"id":800693,"name":"Erica L. Mayer","orcid":"0000-0001-5430-8957","position":9,"is_corresponding":false},{"id":488238,"name":"Stian Knappskog","orcid":"0000-0002-4153-1655","position":10,"is_corresponding":false},{"id":488239,"name":"Per Eystein Lønning","orcid":"0000-0002-8890-6303","position":11,"is_corresponding":false},{"id":91541,"name":"Ursula A. Matulonis","orcid":"0000-0002-3103-6992","position":12,"is_corresponding":false},{"id":98183,"name":"Panagiotis A. Konstantinopoulos","orcid":"0000-0002-1032-1479","position":13,"is_corresponding":false},{"id":75983,"name":"David B. Solit","orcid":"0000-0002-6614-802X","position":14,"is_corresponding":false},{"id":90770,"name":"Helen Won","orcid":"0000-0001-5237-7529","position":15,"is_corresponding":false},{"id":861472,"name":"Hans Petter Eikesdal","orcid":"0000-0003-4086-0147","position":16,"is_corresponding":false},{"id":1821,"name":"Peter J. Park","orcid":"0000-0001-9378-960X","position":17,"is_corresponding":false},{"id":347126,"name":"Gerburg M. Wulf","orcid":"0000-0001-7868-6231","position":18,"is_corresponding":false},{"id":858033,"name":"Felipe Batalini","orcid":"0000-0003-3354-308X","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:54.430249Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}