Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas

Author:

Panwalkar Pooja1ORCID,Tamrazi Benita2ORCID,Dang Derek1ORCID,Chung Chan3ORCID,Sweha Stefan1ORCID,Natarajan Siva Kumar1ORCID,Pun Matthew1ORCID,Bayliss Jill1ORCID,Ogrodzinski Martin P.45,Pratt Drew1ORCID,Mullan Brendan6,Hawes Debra7,Yang Fusheng7ORCID,Lu Chao8ORCID,Sabari Benjamin R.9,Achreja Abhinav1011,Heon Jin1011ORCID,Animasahun Olamide101112ORCID,Cieslik Marcin1,Dunham Christopher1314,Yip Stephen14ORCID,Hukin Juliette15ORCID,Phillips Joanna J.1617ORCID,Bornhorst Miriam1819ORCID,Griesinger Andrea M.2021,Donson Andrew M.2021ORCID,Foreman Nicholas K.2122,Garton Hugh J. L.22ORCID,Heth Jason22ORCID,Muraszko Karin22,Nazarian Javad181923,Koschmann Carl6,Jiang Li24,Filbin Mariella G.24ORCID,Nagrath Deepak1011ORCID,Kool Marcel252627,Korshunov Andrey28,Pfister Stefan M.252629ORCID,Gilbertson Richard J.30,Allis C. David9ORCID,Chinnaiyan Arul M.1ORCID,Lunt Sophia Y.431ORCID,Blüml Stefan2ORCID,Judkins Alexander R.7ORCID,Venneti Sriram16ORCID

Affiliation:

1. Laboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.

2. Department of Radiology, Children’s Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA 90027, USA.

3. Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.

4. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.

5. Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.

6. Department of Pediatrics, Michigan Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

7. Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA 90027, USA.

8. Department of Genetics and Development and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.

9. Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, New York, NY 10065, USA.

10. Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

11. Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.

12. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

13. Division of Anatomic Pathology, British Columbia Children’s Hospital, Vancouver, British Columbia V6H 3N1, Canada.

14. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.

15. Division of Hematology and Oncology, Children’s and Women’s Health Centre of B.C., University of British Columbia, Vancouver, British Columbia V6H 3N1, Canada.

16. Department of Pathology, University of California San Francisco, San Francisco, CA 94132, USA.

17. Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94132, USA.

18. Research Center for Genetic Medicine, Children’s National Health System, Washington, DC 20012, USA.

19. Brain Tumor Institute, Children’s National Health System, Washington, DC 20012, USA.

20. Department of Pediatrics, University of Colorado, Denver, Aurora, CO 80045, USA.

21. Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA.

22. Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.

23. DMG Research Center, Department of Oncology, University Children’s Hospital, CH-8032 Zürich, Switzerland.

24. Department of Pediatric Oncology, Dana-Farber Boston Children’s Cancer and Blood Disorders Center, Boston, MA 02115, USA.

25. Hopp Children’s Cancer Center (KiTZ), Heidelberg 69120, Germany.

26. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg 69120, Germany.

27. Princess Máxima Center for Pediatric Oncology, Utrecht 3584, Netherlands.

28. Department of Neuropathology, German Cancer Research Center (DKFZ), University Hospital Heidelberg and CCU Neuropathology, Heidelberg 69120, Germany.

29. Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany.

30. Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK.

31. Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, USA.

Abstract

Childhood posterior fossa group A ependymomas demonstrate integrated metabolic and epigenetic pathways that can be disrupted by metformin.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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