Genome-wide transcriptome profiling of homologous recombination DNA repair

Guang Peng, Curtis Chun Jen Lin, Wei Mo, Hui Dai, Yun Yong Park, Soo Mi Kim, Yang Peng, Qianxing Mo, Stefan Siwko, Ruozhen Hu, Ju Seog Lee, Bryan Hennessy, Samir Hanash, Gordon Mills, Shiaw Yih Lin

Research output: Contribution to journalArticle

75 Citations (Scopus)

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.

Original languageEnglish (US)
Article number3361
JournalNature Communications
Volume5
DOIs
StatePublished - Feb 20 2014
Externally publishedYes

Fingerprint

Recombinational DNA Repair
genome
Gene Expression Profiling
Repair
deoxyribonucleic acid
Genes
genes
Genome
Defects
cancer
signatures
DNA
defects
Neoplasms
suppressors
network analysis
phenotype
Homologous Recombination
Drug Discovery
Electric network analysis

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Peng, G., Lin, C. C. J., Mo, W., Dai, H., Park, Y. Y., Kim, S. M., ... Lin, S. Y. (2014). Genome-wide transcriptome profiling of homologous recombination DNA repair. Nature Communications, 5, [3361]. https://doi.org/10.1038/ncomms4361

Genome-wide transcriptome profiling of homologous recombination DNA repair. / Peng, Guang; Lin, Curtis Chun Jen; Mo, Wei; Dai, Hui; Park, Yun Yong; Kim, Soo Mi; Peng, Yang; Mo, Qianxing; Siwko, Stefan; Hu, Ruozhen; Lee, Ju Seog; Hennessy, Bryan; Hanash, Samir; Mills, Gordon; Lin, Shiaw Yih.

In: Nature Communications, Vol. 5, 3361, 20.02.2014.

Research output: Contribution to journalArticle

Peng, G, Lin, CCJ, Mo, W, Dai, H, Park, YY, Kim, SM, Peng, Y, Mo, Q, Siwko, S, Hu, R, Lee, JS, Hennessy, B, Hanash, S, Mills, G & Lin, SY 2014, 'Genome-wide transcriptome profiling of homologous recombination DNA repair', Nature Communications, vol. 5, 3361. https://doi.org/10.1038/ncomms4361
Peng, Guang ; Lin, Curtis Chun Jen ; Mo, Wei ; Dai, Hui ; Park, Yun Yong ; Kim, Soo Mi ; Peng, Yang ; Mo, Qianxing ; Siwko, Stefan ; Hu, Ruozhen ; Lee, Ju Seog ; Hennessy, Bryan ; Hanash, Samir ; Mills, Gordon ; Lin, Shiaw Yih. / Genome-wide transcriptome profiling of homologous recombination DNA repair. In: Nature Communications. 2014 ; Vol. 5.
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