دورية أكاديمية
Heterogeneity and transcriptional drivers of triple-negative breast cancer.
| العنوان: | Heterogeneity and transcriptional drivers of triple-negative breast cancer. |
|---|---|
| المؤلفون: | Jovanović B; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Temko D; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA., Stevens LE; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Seehawer M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Fassl A; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Murphy K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Anand J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Garza K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Gulvady A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Qiu X; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Harper NW; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Daniels VW; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Xiao-Yun H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Ge JY; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA., Alečković M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Pyrdol J; Departments of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA., Hinohara K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Egri SB; The Eli and Edythe L. Broad Institute, Cambridge, MA 02142, USA., Papanastasiou M; The Eli and Edythe L. Broad Institute, Cambridge, MA 02142, USA., Vadhi R; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Font-Tello A; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Witwicki R; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Peluffo G; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Trinh A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Shu S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Diciaccio B; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Ekram MB; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Subedee A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Herbert ZT; Department of Molecular Biology Core Facility, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Wucherpfennig KW; Departments of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Departments of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA., Letai AG; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Jaffe JD; The Eli and Edythe L. Broad Institute, Cambridge, MA 02142, USA., Sicinski P; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Brown M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA., Dillon D; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA., Long HW; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Michor F; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA 02142, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: michor@jimmy.harvard.edu., Polyak K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA 02142, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: kornelia_polyak@dfci.harvard.edu. |
| المصدر: | Cell reports [Cell Rep] 2023 Dec 26; Vol. 42 (12), pp. 113564. Date of Electronic Publication: 2023 Dec 14. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| مواضيع طبية MeSH: | Triple Negative Breast Neoplasms*/pathology, Humans ; Transcription Factors/metabolism ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/metabolism |
| مستخلص: | Triple-negative breast cancer (TNBC) is a heterogeneous disease with limited treatment options. To characterize TNBC heterogeneity, we defined transcriptional, epigenetic, and metabolic subtypes and subtype-driving super-enhancers and transcription factors by combining functional and molecular profiling with computational analyses. Single-cell RNA sequencing revealed relative homogeneity of the major transcriptional subtypes (luminal, basal, and mesenchymal) within samples. We found that mesenchymal TNBCs share features with mesenchymal neuroblastoma and rhabdoid tumors and that the PRRX1 transcription factor is a key driver of these tumors. PRRX1 is sufficient for inducing mesenchymal features in basal but not in luminal TNBC cells via reprogramming super-enhancer landscapes, but it is not required for mesenchymal state maintenance or for cellular viability. Our comprehensive, large-scale, multiplatform, multiomics study of both experimental and clinical TNBC is an important resource for the scientific and clinical research communities and opens venues for future investigation. Competing Interests: Declaration of interests The following authors report current employment: Eli Lilly (B.J.), Shasqi, Inc (M.A.), GenieUsGenomics (A.T.), Morrison & Foerster LLP (A.G.), AstraZeneca (M.B.E. and L.E.S.), Odyssey Therapeutics (J.D.J.). K.P. serves on the Scientific Advisory Boards (SABs) of Novartis, Ideaya Biosciences, and Scorpion Therapeutics; holds equity options in Scorpion Therapeutics and Ideaya Biosciences; and receives sponsored research funding from Novartis, where she consults. F.M. is a cofounder of and has equity in Harbinger Health, has equity in Zephyr AI, and consults for Harbinger Health and Zephyr AI. She is on the board of directors of Exscientia Plc. She declares that none of these relationships are directly or indirectly related to the content of this manuscript. P.S. is a consultant for Novartis, Genovis, Guidepoint, The Planning Shop, ORIC Pharmaceuticals, Cedilla Therapeutics, Syros Pharmaceuticals, Blueprint Medicines, Curie Bio, Differentiated Therapeutics, Excientia, Ligature Therapeutics, Merck, Redesign Science, Sibylla Biotech, and Exo Therapeutics; he receives research funding from Novartis. A.G.L. serves on the SAB of Flash Therapeutics, Zentalis Pharmaceuticals, and Trueline Therapeutics and consults for AbbVie. M.B. receives research funding from Novartis, where he also serves on the SAB and acts as a consultant. He is a member of the SAB for Kronos Bio and GV20 Therapeutics and holds equity in both companies. He also serves on the SAB for FibroGen and is a consultant for Belharra Therapeutics. K.W.W. serves on the SAB of TScan Therapeutics, SQZ Biotech, Bisou Bioscience Company, DEM BioPharma, and Nextechinvest; receives sponsored research funding from Novartis; and is a co-founder, stockholder, and advisory board member of Immunitas Therapeutics. D.D. receives research support from Canon, Inc. H.W.L. receives research funding from Novartis. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
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| معلومات مُعتمدة: | R35 CA242427 United States CA NCI NIH HHS; R35 CA197623 United States CA NCI NIH HHS; P50 CA168504 United States CA NCI NIH HHS; U54 CA193461 United States CA NCI NIH HHS; P01 CA250959 United States CA NCI NIH HHS; R01 CA251599 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: CP: Cancer; triple-negative breast cancer; tumor heterogeneity |
| المشرفين على المادة: | 0 (Transcription Factors) 0 (PRRX1 protein, human) 0 (Homeodomain Proteins) |
| تواريخ الأحداث: | Date Created: 20231215 Date Completed: 20240101 Latest Revision: 20240604 |
| رمز التحديث: | 20240604 |
| مُعرف محوري في PubMed: | PMC10842760 |
| DOI: | 10.1016/j.celrep.2023.113564 |
| PMID: | 38100350 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2023.113564 |