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The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Malta, Tathiane M ; Sabedot, Thais S ; Morosini, Natalia S ; Datta, Indrani ; Garofano, Luciano ; Vallentgoed, Wies ; Varn, Frederick S ; Aldape, Kenneth ; D'Angelo, Fulvio ; Bakas, Spyridon ; Barnholtz-Sloan, Jill S ; Gan, Hui K ; Hasanain, Mohammad ; Hau, Ann-Christin ; Johnson, Kevin C ; Cazacu, Simona ; deCarvalho, Ana C ; Khasraw, Mustafa ; Kocakavuk, Emre ; Kouwenhoven, Mathilde C M ; Migliozzi, Simona ; Niclou, Simone P ; Niers, Johanna M ; Ormond, D Ryan ; Paek, Sun Ha ; Reifenberger, Guido ; Sillevis Smitt, Peter A ; Smits, Marion ; Stead, Lucy F ; van den Bent, Martin J ; Van Meir, Erwin G ; Walenkamp, Annemiek ; Weiss, Tobias ; Weller, Michael ; Westerman, Bart A ; Ylstra, Bauke ; Wesseling, Pieter ; Lasorella, Anna ; French, Pim J ; Poisson, Laila M ; Verhaak, Roel G W ; Iavarone, Antonio ; Noushmehr, Houtan

Cancer research (Chicago, Ill.), 2024-03, Vol.84 (5), p.741-756 [Periódico revisado por pares]

United States: American Association for Cancer Research

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Título:
The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen
Autor: Malta, Tathiane M ; Sabedot, Thais S ; Morosini, Natalia S ; Datta, Indrani ; Garofano, Luciano ; Vallentgoed, Wies ; Varn, Frederick S ; Aldape, Kenneth ; D'Angelo, Fulvio ; Bakas, Spyridon ; Barnholtz-Sloan, Jill S ; Gan, Hui K ; Hasanain, Mohammad ; Hau, Ann-Christin ; Johnson, Kevin C ; Cazacu, Simona ; deCarvalho, Ana C ; Khasraw, Mustafa ; Kocakavuk, Emre ; Kouwenhoven, Mathilde C M ; Migliozzi, Simona ; Niclou, Simone P ; Niers, Johanna M ; Ormond, D Ryan ; Paek, Sun Ha ; Reifenberger, Guido ; Sillevis Smitt, Peter A ; Smits, Marion ; Stead, Lucy F ; van den Bent, Martin J ; Van Meir, Erwin G ; Walenkamp, Annemiek ; Weiss, Tobias ; Weller, Michael ; Westerman, Bart A ; Ylstra, Bauke ; Wesseling, Pieter ; Lasorella, Anna ; French, Pim J ; Poisson, Laila M ; Verhaak, Roel G W ; Iavarone, Antonio ; Noushmehr, Houtan
Assuntos: Brain Neoplasms - pathology ; Cancer Landscapes ; CNS Cancers ; Epigenesis, Genetic ; Epigenetics ; Epigenomics ; Glioma - pathology ; Humans ; Isocitrate Dehydrogenase - genetics ; Isocitrate Dehydrogenase - metabolism ; Mutation ; Neoplasm Recurrence, Local - genetics ; Tumor Evolution ; Tumor Microenvironment
É parte de: Cancer research (Chicago, Ill.), 2024-03, Vol.84 (5), p.741-756
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
T.M Malta and T.S. Sabedot are the co-first authors of this article.
A list of participants and their affiliations for The GLASS Consortium is available in the Supplementary Appendix.
R.G.W. Verhaak, A. Iavarone, and H. Noushmehr are the co-senior authors of this article.
Cancer Res 2024;84:741–56
N.S Morosini, I. Datta, L. Garofano, W. Vallentgoed, and F.S. Varn are the co-second authors of this article.
Descrição: 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 histologic 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 neoangiogenesis 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 toward an IDHwt-like phenotype. Standard treatments are related to loss of DNA methylation in IDHmut glioma, resulting in epigenetic activation of genes associated with tumor progression and alterations in the microenvironment that resemble treatment-naïve IDHwt glioma.
Editor: United States: American Association for Cancer Research
Idioma: Inglês

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The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

United States: American Association for Cancer Research

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