Prognostic Significance of DNA Methylation Profiles at MRI Enhancing Tumor Recurrence: a Report from the EORTC 26091 TAVAREC Trial - Sorbonne Université Access content directly
Journal Articles Clinical Cancer Research Year : 2022

Prognostic Significance of DNA Methylation Profiles at MRI Enhancing Tumor Recurrence: a Report from the EORTC 26091 TAVAREC Trial

Kaspar Draaisma
  • Function : Author
C. Mircea S. Tesileanu
Iris de Heer
  • Function : Author
Martin Klein
Marion Smits
  • Function : Author
Jaap Reijneveld
  • Function : Author
Paul Clement
Filip Y.F. de Vos
Antje Wick
  • Function : Author
Paul Mulholland
Martin J.B. Taphoorn
  • Function : Author
Michael Weller
Olivier Chinot
Johan Kros
Tina Verschuere
  • Function : Author
Corneel Coens
  • Function : Author
Vassilis Golfinopoulos
Thierry Gorlia
  • Function : Author
Pierre Robe
Martin van den Bent
Pim French

Abstract

Purpose: Despite recent advances in the molecular characterization of gliomas, it remains unclear which patients benefit most from which second-line treatments. The TAVAREC trial was a randomized, open-label phase II trial assessing the benefit of the addition of the angiogenesis inhibitor bevacizumab to treatment with temozolomide in patients with a first enhancing recurrence of World Health Organization grade 2 or 3 glioma without 1p/19q codeletion. We evaluated the prognostic significance of genome-wide DNA methylation profiles and copy-number variations on the TAVAREC trial samples. Experimental design: Isocitrate dehydrogenase (IDH) mutation status was determined via Sanger sequencing and IHC. DNA methylation analysis was performed using the MethylationEPIC BeadChip (Illumina) from which 1p/19q codeletion, MGMT promoter methylation (MGMT-STP27), and homozygous deletion of CDKN2A/B were determined. DNA methylation classes were determined according to classifiers developed in Heidelberg and The Cancer Genome Atlas (TCGA; "Heidelberg" and "TCGA" classifier respectively). Results: DNA methylation profiles of 122 samples were successfully determined. As expected, most samples were IDH-mutant (89/122) and MGMT promotor methylated (89/122). Methylation classes were prognostic for time to progression. However, Heidelberg methylation classes determined at time of diagnosis were no longer prognostic following enhancing recurrence of the tumor. In contrast, TCGA methylation classes of primary samples remained prognostic also following enhancing recurrence. Homozygous deletions in CDKN2A/B were found in 10 of 87 IDH-mutated samples and were prognostically unfavorable at recurrence. Conclusions: DNA methylome Heidelberg classification at time of diagnosis is no longer of prognostic value at the time of enhancing recurrence. CDKN2A/B deletion status was predictive of survival from progression of IDH-mutated tumors.

Dates and versions

hal-04577240 , version 1 (16-05-2024)

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Kaspar Draaisma, C. Mircea S. Tesileanu, Iris de Heer, Martin Klein, Marion Smits, et al.. Prognostic Significance of DNA Methylation Profiles at MRI Enhancing Tumor Recurrence: a Report from the EORTC 26091 TAVAREC Trial. Clinical Cancer Research, 2022, 28 (11), pp.2440-2448. ⟨10.1158/1078-0432.CCR-21-3725⟩. ⟨hal-04577240⟩
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