Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma.

Autor:	El Zarif T; Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA., Semaan K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA., Eid M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA., Seo JH; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA., Garinet S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Davidsohn MP; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Sahgal P; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Fortunato B; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Canniff J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Nassar AH; Section of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA., Abou Alaiwi S; Section of Cardiology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA., Bakouny Z; Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Lakshminarayanan G; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Savignano H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Lyons K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Matar S; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Ali A; Department of Medicine, University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA., Saad E; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Saliby RM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Cordeiro P; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA., Zhang Z; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., El Ahmar N; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Laimon YN; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Labaki C; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Shah V; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Freeman D; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., O'Toole J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Lee GM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Hwang J; Department of Medicine, University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA., Pomerantz M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Signoretti S; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Van Allen EM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA., Xie W; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA., Berchuck JE; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Viswanathan SR; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Braun DA; Section of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA., Choueiri TK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: toni_choueiri@dfci.harvard.edu., Freedman ML; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: matthew_freedman@dfci.harvard.edu., Baca SC; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA, USA. Electronic address: sylvan_baca@dfci.harvard.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Jun 25; Vol. 43 (6), pp. 114350. Date of Electronic Publication: 2024 Jun 12.
DOI:	10.1016/j.celrep.2024.114350
Abstrakt:	Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy. Competing Interests: Declaration of interests S.R.V. reports consulting (current or past 3 years) for Jnana Therapeutics, research support from Bayer, and that their spouse is an employee of and holds equity in Kojin Therapeutics. D.A.B. reports honoraria from LM Education/Exchange Services; advisory board fees from Exelixis and AVEO; consulting fees from Merck, Pfizer, and Elephas; equity in Elephas, Fortress Biotech (subsidiary), and CurIOS Therapeutics; personal fees from Schlesinger Associates, Cancer Expert Now, Adnovate Strategies, MDedge, CancerNetwork, Catenion, OncLive, Cello Health BioConsulting, PWW Consulting, Haymarket Medical Network, Aptitude Health, ASCO Post/Harborside, Targeted Oncology, Accolade 2nd.MD, DLA Piper, AbbVie, Compugen, Link Cell Therapies, and Scholar Rock; and research support from Exelixis and AstraZeneca, outside of the submitted work. S.C.B., T.K.C., and M.L.F. are co-founders and shareholders of Precede Biosciences. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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