TY  - JOUR
AU  - Zhu, Rong
AU  - Eason, Katherine
AU  - Chin, Suet-Feung
AU  - Edwards, Paul A W
AU  - Manzano Garcia, Raquel
AU  - Moulange, Richard
AU  - Pan, Jia Wern
AU  - Teo, Soo Hwang
AU  - Mukherjee, Sach
AU  - Callari, Maurizio
AU  - Caldas, Carlos
AU  - Sammut, Stephen-John
AU  - Rueda, Oscar M
TI  - Detecting homologous recombination deficiency for breast cancer through integrative analysis of genomic data.
JO  - Molecular oncology
VL  - 19
IS  - 12
SN  - 1574-7891
CY  - Hoboken, NJ
PB  - John Wiley & Sons, Inc.
M1  - DZNE-2025-01351
SP  - 3613 - 3633
PY  - 2025
AB  - Homologous 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.
KW  - Humans
KW  - Breast Neoplasms: genetics
KW  - Breast Neoplasms: drug therapy
KW  - Female
KW  - Genomics: methods
KW  - Homologous Recombination: genetics
KW  - DNA Copy Number Variations
KW  - Cell Line, Tumor
KW  - Poly(ADP-ribose) Polymerase Inhibitors: pharmacology
KW  - Polymorphism, Single Nucleotide
KW  - Mutation
KW  - breast cancer (Other)
KW  - cancer genomics (Other)
KW  - genomic data integration (Other)
KW  - homologous recombination deficiency (Other)
KW  - semi‐supervised learning (Other)
KW  - tumour biomarkers (Other)
KW  - Poly(ADP-ribose) Polymerase Inhibitors (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40260608
DO  - DOI:10.1002/1878-0261.70041
UR  - https://pub.dzne.de/record/282593
ER  -