Integrating Multi-omics Data to Dissect Mechanisms of DNA repair Dysregulation in Breast Cancer.
DNA repair genes and pathways that are transcriptionally dysregulated in cancer provide the first line of evidence for the altered DNA repair status in tumours, and hence have been explored intensively as a source for biomarker discovery. The molecular mechanisms underlying DNA repair dysregulation, however, have not been systematically investigated in any cancer type. In this study, we performed a statistical analysis to dissect the roles of DNA copy number alteration (CNA), DNA methylation (DM) at gene promoter regions and the expression changes of transcription factors (TFs) in the differential expression of individual DNA repair genes in normal versus tumour breast samples. These gene-level results were summarised at pathway level to assess whether different DNA repair pathways are affected in distinct manners. Our results suggest that CNA and expression changes of TFs are major causes of DNA repair dysregulation in breast cancer, and that a subset of the identified TFs may exert global impacts on the dysregulation of multiple repair pathways. Our work hence provides novel insights into DNA repair dysregulation in breast cancer. These insights improve our understanding of the molecular basis of the DNA repair biomarkers identified thus far, and have potential to inform future biomarker discovery.
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4067, Australia.
Chao
C
Liu
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.
Florian
F
Rohart
UQ Centre for Clinical Research and School of Medicine, The University of Queensland, Herston, QLD 4101, Australia.
Peter T
PT
Simpson
QIMR-Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia.
Kum Kum
KK
Khanna
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4067, Australia.
Mark A
MA
Ragan
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.
Kim-Anh
KA
Lê Cao
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