Advancing biology-based therapeutic approaches for atypical teratoid rhabdoid tumors

Author:

Hoffman Lindsey M1,Richardson Elizabeth Anne234,Ho Ben234,Margol Ashley56,Reddy Alyssa7,Lafay-Cousin Lucie89,Chi Susan101112,Slavc Irene1314,Judkins Alexander151617,Hasselblatt Martin18,Bourdeaut Franck192021,Frühwald Michael C222324,Vibhakar Rajeev252627,Bouffet Eric282930,Huang Annie293031

Affiliation:

1. Center for Cancer and Blood Disorders, Phoenix Children’s Hospital, Phoenix, Arizona, USA

2. Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada

3. Department of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada

4. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

5. Cancer and Blood Disease Institute, Children’s Hospital Los Angeles, Los Angeles, California, USA

6. Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California, USA

7. Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, California, USA

8. Department of Pediatric Hematology Oncology and Blood and Marrow Transplantation, Alberta Children’s Hospital, Calgary, Alberta, Canada

9. Department of Paediatrics and Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

10. Pediatric Medical Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

11. Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, Massachusetts, USA

12. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA

13. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

14. Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

15. Center for Personalized Medicine, Children’s Hospital of Los Angeles

16. Pathology and Laboratory Medicine, Children’s Hospital of Los Angeles

17. Department of Pathology, Keck School of Medicine University of Southern California, Los Angeles, California, USA

18. Institute of Neuropathology, University Hospital Münster, Münster, Germany

19. Curie Institute, Integrated Cancer Research Site, Paris, France

20. Departments of Genetics and of Oncopediatry and Young Adults, Curie Institute, Paris, France

21. INSERM U830, Laboratory of Translational Research in Pediatric Oncology, SIREDO Pediatric Oncology Center, Curie Institute, Paris, France

22. Swabian Children’s Cancer Center, University Children’s Hospital, University Hospital Augsburg, Augsburg, Germany

23. Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster, University of Münster, Münster, Germany

24. EU-RHAB Registry Working Group, Augsburg, Germany

25. Department of Pediatrics, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA

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

27. Department of Neurosurgery, University of Colorado Denver, Aurora, Colorado, USA

28. Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada

29. Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada

30. Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada

31. Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Abstract

AbstractAtypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant central nervous system cancer arising in infants and younger children, historically considered to be homogeneous, monogenic, and incurable. Recent use of intensified therapies has modestly improved survival for ATRT; however, a majority of patients will still succumb to their disease. While ATRTs almost universally exhibit loss of SMARCB1 (BAF47/INI1/SNF5), recent whole genome, transcriptome, and epigenomic analyses of large cohorts reveal previously underappreciated molecular heterogeneity. These discoveries provide novel insights into how SMARCB1 loss drives oncogenesis and confer specific therapeutic vulnerabilities, raising exciting prospects for molecularly stratified treatment for patients with ATRT.

Funder

Canadian Cancer Society Research Institute Impact

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Neurology (clinical),Oncology

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