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 B. Mills, Shiaw Yih Lin

    Research output: Contribution to journalArticle

    94 Scopus citations

    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

    ASJC Scopus subject areas

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

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  • Cite this

    Peng, G., Lin, C. C. J., Mo, W., Dai, H., Park, Y. Y., Kim, S. M., Peng, Y., Mo, Q., Siwko, S., Hu, R., Lee, J. S., Hennessy, B., Hanash, S., Mills, G. B., & Lin, S. Y. (2014). Genome-wide transcriptome profiling of homologous recombination DNA repair. Nature communications, 5, [3361]. https://doi.org/10.1038/ncomms4361