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@ARTICLE{Zhu:282593,
author = {Zhu, Rong and Eason, Katherine and Chin, Suet-Feung and
Edwards, Paul A W and Manzano Garcia, Raquel and Moulange,
Richard and Pan, Jia Wern and Teo, Soo Hwang and Mukherjee,
Sach and Callari, Maurizio and Caldas, Carlos and Sammut,
Stephen-John and Rueda, Oscar M},
title = {{D}etecting homologous recombination deficiency for breast
cancer through integrative analysis of genomic data.},
journal = {Molecular oncology},
volume = {19},
number = {12},
issn = {1574-7891},
address = {Hoboken, NJ},
publisher = {John Wiley $\&$ Sons, Inc.},
reportid = {DZNE-2025-01351},
pages = {3613 - 3633},
year = {2025},
abstract = {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.},
keywords = {Humans / Breast Neoplasms: genetics / Breast Neoplasms:
drug therapy / Female / Genomics: methods / Homologous
Recombination: genetics / DNA Copy Number Variations / Cell
Line, Tumor / Poly(ADP-ribose) Polymerase Inhibitors:
pharmacology / Polymorphism, Single Nucleotide / Mutation /
breast cancer (Other) / cancer genomics (Other) / genomic
data integration (Other) / homologous recombination
deficiency (Other) / semi‐supervised learning (Other) /
tumour biomarkers (Other) / Poly(ADP-ribose) Polymerase
Inhibitors (NLM Chemicals)},
cin = {AG Mukherjee},
ddc = {610},
cid = {I:(DE-2719)1013030},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40260608},
doi = {10.1002/1878-0261.70041},
url = {https://pub.dzne.de/record/282593},
}