dc.contributor.author | Batalini, Felipe | |
dc.contributor.author | Gulhan, Doga C. | |
dc.contributor.author | Mao, Victor | |
dc.contributor.author | Tran, Antuan | |
dc.contributor.author | Polak, Madeline | |
dc.contributor.author | Xiong, Niya | |
dc.contributor.author | Tayob, Nabihah | |
dc.contributor.author | Tung, Nadine M. | |
dc.contributor.author | Winer, Eric P. | |
dc.contributor.author | Mayer, Erica L. | |
dc.contributor.author | Knappskog, Stian | |
dc.contributor.author | Lønning, Per Eystein | |
dc.contributor.author | Matulonis, Ursula A. | |
dc.contributor.author | Konstantinopoulos, Panagiotis A. | |
dc.contributor.author | Solit, David B. | |
dc.contributor.author | Won, Helen | |
dc.contributor.author | Eikesdal, Hans Petter | |
dc.contributor.author | Park, Peter J. | |
dc.contributor.author | Wulf, Gerburg M. | |
dc.date.accessioned | 2023-01-24T07:57:24Z | |
dc.date.available | 2023-01-24T07:57:24Z | |
dc.date.created | 2022-12-02T13:36:07Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://hdl.handle.net/11250/3045634 | |
dc.description.abstract | Purpose:
The identification of patients with homologous recombination deficiency (HRD) beyond BRCA1/2 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.
Experimental Design:
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).
Results:
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.
Conclusions:
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 BRCA1/2mut who might benefit from PARP inhibitors. Prospective clinical utility testing is warranted. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | American Association for Cancer Research | en_US |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/deed.no | * |
dc.title | Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2022 The Authors | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-22-0749 | |
dc.identifier.cristin | 2087784 | |
dc.source.journal | Clinical Cancer Research | en_US |
dc.source.pagenumber | 4714-4723 | en_US |
dc.identifier.citation | Clinical Cancer Research. 2022, 28 (21), 4714-4723. | en_US |
dc.source.volume | 28 | en_US |
dc.source.issue | 21 | en_US |