دورية أكاديمية
Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns.
| العنوان: | Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns. |
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| المؤلفون: | 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. |
| المصدر: | Cell [Cell] 2018 Apr 05; Vol. 173 (2), pp. 499-514.e23. Date of Electronic Publication: 2018 Mar 22. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, Ma : Cell Press Original Publication: Cambridge, MIT Press. |
| مواضيع طبية MeSH: | Aneuploidy*, Neoplasms/*pathology, Animals ; Cell Line, Tumor ; Cell Proliferation ; Chromosome Mapping ; Chromosomes/genetics ; E2F1 Transcription Factor/antagonists & inhibitors ; E2F1 Transcription Factor/genetics ; E2F1 Transcription Factor/metabolism ; Female ; Gene Library ; Genomics ; Humans ; Keratins/metabolism ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Oncogenes ; Open Reading Frames/genetics ; RNA Interference ; RNA, Small Interfering/metabolism |
| مستخلص: | 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. (Copyright © 2018 Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Nat Methods. 2018 Jun;15(6):408. (PMID: 29855584) |
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| معلومات مُعتمدة: | United States HHMI Howard Hughes Medical Institute; R01 CA178039 United States CA NCI NIH HHS; P30 CA125123 United States CA NCI NIH HHS; R00 CA212621 United States CA NCI NIH HHS; K99 CA212621 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: KRTAP; ORF screens; SCNA; aneuploidy; cancer drivers; gain of function screens; genetic screens; proliferation; tissue specificity |
| المشرفين على المادة: | 0 (E2F1 Transcription Factor) 0 (E2F1 protein, human) 0 (RNA, Small Interfering) 68238-35-7 (Keratins) |
| تواريخ الأحداث: | Date Created: 20180327 Date Completed: 20190208 Latest Revision: 20231104 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6643283 |
| DOI: | 10.1016/j.cell.2018.02.037 |
| PMID: | 29576454 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4172 |
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| DOI: | 10.1016/j.cell.2018.02.037 |