Integrating multi-omics data to dissect mechanisms of DNA repair dysregulation in breast cancer

Liu, Chao, Rohart, Florian, Simpson, Peter T., Khanna, Kum Kum, Ragan, Mark A. and Le Cao, Kim-Anh (2016) Integrating multi-omics data to dissect mechanisms of DNA repair dysregulation in breast cancer. Scientific Reports, 6 34000.1-34000.11. doi:10.1038/srep34000


Author Liu, Chao
Rohart, Florian
Simpson, Peter T.
Khanna, Kum Kum
Ragan, Mark A.
Le Cao, Kim-Anh
Title Integrating multi-omics data to dissect mechanisms of DNA repair dysregulation in breast cancer
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2016-09-26
Year available 2016
Sub-type Article (original research)
DOI 10.1038/srep34000
Open Access Status DOI
Volume 6
Start page 34000.1
End page 34000.11
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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