title: Genome-wide transcriptome profiling of homologous recombination DNA repair.
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.
authors.affiliation: 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].
authors.forename: Guang
authors.initials: G
authors.lastname: Peng
authors.affiliation: 1] Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA [2].
authors.forename: Curtis
authors.initials: C
authors.lastname: Chun-Jen Lin
authors.affiliation: 1] Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA [2].
authors.forename: Wei
authors.initials: W
authors.lastname: Mo
authors.affiliation: Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Yun-Yong
authors.initials: YY
authors.lastname: Park
authors.affiliation: Department of Physiology, Chonbuk National University Medical School, Jeonju 561-181, Republic of Korea.
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Qianxing
authors.initials: Q
authors.lastname: Mo
authors.affiliation: Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Siwko
authors.affiliation: Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Ruozhen
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
authors.forename: Bryan
authors.initials: B
authors.lastname: Hennessy
authors.affiliation: Department of Clinical Cancer Prevention, Unit 1013, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: Hanash
authors.affiliation: Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Shiaw-Yih
authors.initials: SY
authors.lastname: Lin
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics; D059767:Recombinational DNA Repair / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D051059:PTEN Phosphohydrolase