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Nat Commun. 2014;5:3361. doi: 10.1038/ncomms4361.

Genome-wide transcriptome profiling of homologous recombination DNA repair.

Author information

1
1] Department of Clinical Cancer Prevention, Unit 1013, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Department of Oncology, Tongji Hospital, Tongji Medical College, The University of Huazhong Science & Technology, Wuhan, Hubei Province 430022, China [3].
2
1] Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA [2].
3
Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
4
Department of Physiology, Chonbuk National University Medical School, Jeonju 561-181, Republic of Korea.
5
Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
6
Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
7
Department of Clinical Cancer Prevention, Unit 1013, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Abstract

Homologous recombination (HR) repair deficiency predisposes to cancer development, but also sensitizes cancer cells to DNA damage-inducing therapeutics. Here we identify an HR defect (HRD) gene signature that can be used to functionally assess HR repair status without interrogating individual genetic alterations in cells. By using this HRD gene signature as a functional network analysis tool, we discover that simultaneous loss of two major tumour suppressors BRCA1 and PTEN extensively rewire the HR repair-deficient phenotype, which is found in cells with defects in either BRCA1 or PTEN alone. Moreover, the HRD gene signature serves as an effective drug discovery platform to identify agents targeting HR repair as potential chemo/radio sensitizers. More importantly, this HRD gene signature is able to predict clinical outcomes across multiple cancer lineages. Our findings, therefore, provide a molecular profile of HR repair to assess its status at a functional network level, which can provide both biological insights and have clinical implications in cancer.

PMID:
24553445
PMCID:
PMC4017859
DOI:
10.1038/ncomms4361
[Indexed for MEDLINE]
Free PMC Article

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