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Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns.
Sack, Laura Magill; Davoli, Teresa; Li, Mamie Z; Li, Yuyang; Xu, Qikai; Naxerova, Kamila; Wooten, Eric C; Bernardi, Ronald J; Martin, Timothy D; Chen, Ting; Leng, Yumei; Liang, Anthony C; Scorsone, Kathleen A; Westbrook, Thomas F; Wong, Kwok-Kin; Elledge, Stephen J.
Affiliation
  • Sack LM; Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  • Davoli T; Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  • Li MZ; Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  • Li Y; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, China.
  • Xu Q; Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  • Naxerova K; Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  • Wooten EC; Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  • Bernardi RJ; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Human Genetics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Martin TD; Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  • Chen T; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
  • Leng Y; Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  • Liang AC; Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  • Scorsone KA; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Human Genetics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Westbrook TF; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Human Genetics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Wong KK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
  • Elledge SJ; Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: selledge@genetics.med.harvard.edu.
Cell ; 173(2): 499-514.e23, 2018 04 05.
Article in En | MEDLINE | ID: mdl-29576454
ABSTRACT
Genomics has provided a detailed structural description of the cancer genome. Identifying oncogenic drivers that work primarily through dosage changes is a current challenge. Unrestrained proliferation is a critical hallmark of cancer. We constructed modular, barcoded libraries of human open reading frames (ORFs) and performed screens for proliferation regulators in multiple cell types. Approximately 10% of genes regulate proliferation, with most performing in an unexpectedly highly tissue-specific manner. Proliferation drivers in a given cell type showed specific enrichment in somatic copy number changes (SCNAs) from cognate tumors and helped predict aneuploidy patterns in those tumors, implying that tissue-type-specific genetic network architectures underlie SCNA and driver selection in different cancers. In vivo screening confirmed these results. We report a substantial contribution to the catalog of SCNA-associated cancer drivers, identifying 147 amplified and 107 deleted genes as potential drivers, and derive insights about the genetic network architecture of aneuploidy in tumors.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aneuploidy / Neoplasms Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2018 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aneuploidy / Neoplasms Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2018 Type: Article Affiliation country: United States