The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen-Reference-Cited by-同舟云学术

The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen

Published:2023-12-20 Issue: Volume: Page:
ISSN:0008-5472
Container-title:Cancer Research
language:en
Short-container-title:

Author:

Malta Tathiane M.¹^ORCID,Sabedot Thais S.²^ORCID,Morosini Natalia S.³^ORCID,Datta Indrani⁴^ORCID,Garofano Luciano⁵^ORCID,Vallentgoed Wies R.⁶^ORCID,Varn Frederick S.⁷^ORCID,Aldape Kenneth⁸^ORCID,D'Angelo Fulvio⁹^ORCID,Bakas Spyridon¹⁰^ORCID,Barnholtz-Sloan Jill S.¹¹^ORCID,Gan Hui K.¹²^ORCID,Hasanain Mohammad¹³^ORCID,Hau Ann-Christin¹⁴^ORCID,Johnson Kevin C.¹⁵^ORCID,Cazacu Simona¹⁶^ORCID,deCarvalho Ana C.¹⁶^ORCID,Khasraw Mustafa¹⁷^ORCID,Kocakavuk Emre¹⁸^ORCID,Kouwenhoven Mathilde C.M.¹⁹^ORCID,Migliozzi Simona²⁰^ORCID,Niclou Simone P.²¹^ORCID,Niers Johanna M.²²^ORCID,Ormond D. Ryan.²³^ORCID,Paek Sun Ha²⁴^ORCID,Reifenberger Guido²⁵^ORCID,Sillevis Smitt Peter A.²⁶^ORCID,Smits Marion²⁶^ORCID,Stead Lucy F.²⁷^ORCID,van den Bent Martin J.⁶^ORCID,Van Meir Erwin G.²⁸^ORCID,Walenkamp Annemiek²⁹^ORCID,Weiss Tobias³⁰^ORCID,Weller Michael³⁰^ORCID,Westerman Bart A.³¹^ORCID,Ylstra Bauke³¹^ORCID,Wesseling Pieter³²^ORCID,Lasorella Anna³³^ORCID,French Pim J.²⁶^ORCID,Poisson Laila M.¹⁶^ORCID,Consortium The GLASS³⁴,Verhaak Roel G.W.³⁵^ORCID,Iavarone Antonio²⁰^ORCID,Noushmehr Houtan³^ORCID

Affiliation:

1. School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil

2. Henry Ford Health System, Detroit, MI, United States

3. Henry Ford Health System, Detroit, Michigan, United States

4. Henry Ford Health System, United States

5. Sylvester Comprehensive Cancer Center, University of Miami, Miami, United States

6. Erasmus MC Cancer Institute, Rotterdam, Netherlands

7. The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States

8. National Cancer Institute, Bethesda, Maryland, United States

9. University of Miami, Miami, Florida, United States

10. Indiana University – Purdue University Indianapolis, Indianapolis, Indiana, United States

11. National Cancer Institute, Rockville, MD, United States

12. Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia

13. Columbia University Medical Center, Miami, FL, United States

14. University Hospital Frankfurt, Goethe University, Frankfurt am Main - Niederrad, Germany

15. Jackson Laboratory for Genomic Medicine, United States

16. Henry Ford Hospital, Detroit, Michigan, United States

17. Duke University, Durham, NC, United States

18. Yale School of Medicine, New Haven, CT, United States

19. Amsterdam University Medical Centers, Amsterdam, Noord-Holland, Netherlands

20. Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, United States

21. University of Luxembourg, Esch-sur-Alzette, Luxembourg

22. Department of Neurology/Cancer CenterAmsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Netherlands

23. University of Colorado Anschutz Medical Campus, Aurora, CO, United States

24. Seoul National University College of Medicine, Seoul, Korea (South), Republic of

25. Heinrich Heine University Düsseldorf, Duesseldorf, Germany

26. Erasmus MC, Rotterdam, Netherlands

27. University of Leeds, Leeds, United Kingdom

28. University of Alabama at Birmingham, Birmingham, GA, United States

29. University Medical Center Groningen, University of Groningen, Groningen, Netherlands

30. University Hospital of Zurich, Zurich, Switzerland

31. Amsterdam UMC Location VUmc, Amsterdam, Netherlands

32. Amsterdam University Medical Centers, Netherlands

33. University of Miami, Miami, FL, United States

34. Glioma Longitudinal AnalySiS, United States

35. Yale School of Medicine, Farmington, CT, United States

Abstract

Abstract Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histological progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neo-angiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution towards an IDHwt-like phenotype.

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

Link

https://aacrjournals.org/cancerres/article-pdf/doi/10.1158/0008-5472.CAN-23-2093/3392055/can-23-2093.pdf