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000282593 1001_ $$00000-0002-7758-4409$$aZhu, Rong$$b0
000282593 245__ $$aDetecting homologous recombination deficiency for breast cancer through integrative analysis of genomic data.
000282593 260__ $$aHoboken, NJ$$bJohn Wiley & Sons, Inc.$$c2025
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000282593 520__ $$aHomologous recombination deficiency (HRD) leads to genomic instability, and patients with HRD can benefit from HRD-targeting therapies. Previous studies have primarily focused on identifying HRD biomarkers using data from a single technology. Here we integrated features from different genomic data types, including total copy number (CN), allele-specific copy number (ASCN) and single nucleotide variants (SNV). Using a semi-supervised method, we developed HRD classifiers from 1404 breast tumours across two datasets based on their BRCA1/2 status, demonstrating improved HRD identification when aggregating different data types. Notably, HRD-positive tumours in ER-negative disease showed improved survival post-adjuvant chemotherapy, while HRD status strongly correlated with neoadjuvant treatment response. Furthermore, our analysis of cell lines highlighted a sensitivity to PARP inhibitors, particularly rucaparib, among predicted HRD-positive lines. Exploring somatic mutations outside BRCA1/2, we confirmed variants in several genes associated with HRD. Our method for HRD classification can adapt to different data types or resolutions and can be used in various scenarios to help refine patient selection for HRD-targeting therapies that might lead to better clinical outcomes.
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000282593 650_7 $$2Other$$abreast cancer
000282593 650_7 $$2Other$$acancer genomics
000282593 650_7 $$2Other$$agenomic data integration
000282593 650_7 $$2Other$$ahomologous recombination deficiency
000282593 650_7 $$2Other$$asemi‐supervised learning
000282593 650_7 $$2Other$$atumour biomarkers
000282593 650_7 $$2NLM Chemicals$$aPoly(ADP-ribose) Polymerase Inhibitors
000282593 650_2 $$2MeSH$$aHumans
000282593 650_2 $$2MeSH$$aBreast Neoplasms: genetics
000282593 650_2 $$2MeSH$$aBreast Neoplasms: drug therapy
000282593 650_2 $$2MeSH$$aFemale
000282593 650_2 $$2MeSH$$aGenomics: methods
000282593 650_2 $$2MeSH$$aHomologous Recombination: genetics
000282593 650_2 $$2MeSH$$aDNA Copy Number Variations
000282593 650_2 $$2MeSH$$aCell Line, Tumor
000282593 650_2 $$2MeSH$$aPoly(ADP-ribose) Polymerase Inhibitors: pharmacology
000282593 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide
000282593 650_2 $$2MeSH$$aMutation
000282593 7001_ $$aEason, Katherine$$b1
000282593 7001_ $$aChin, Suet-Feung$$b2
000282593 7001_ $$aEdwards, Paul A W$$b3
000282593 7001_ $$aManzano Garcia, Raquel$$b4
000282593 7001_ $$00000-0003-1827-0941$$aMoulange, Richard$$b5
000282593 7001_ $$aPan, Jia Wern$$b6
000282593 7001_ $$aTeo, Soo Hwang$$b7
000282593 7001_ $$0P:(DE-2719)2811372$$aMukherjee, Sach$$b8$$udzne
000282593 7001_ $$aCallari, Maurizio$$b9
000282593 7001_ $$00000-0003-3547-1489$$aCaldas, Carlos$$b10
000282593 7001_ $$aSammut, Stephen-John$$b11
000282593 7001_ $$00000-0003-0008-4884$$aRueda, Oscar M$$b12
000282593 773__ $$0PERI:(DE-600)2322586-5$$a10.1002/1878-0261.70041$$gVol. 19, no. 12, p. 3613 - 3633$$n12$$p3613 - 3633$$tMolecular oncology$$v19$$x1574-7891$$y2025
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