Heterogeneity of DNA methylation profiles and copy number alterations in 10782 adult-type glioblastomas, IDH-wildtype

Authors

  • David E. Reuss Department of Neuropathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Daniel Schrimpf Department of Neuropathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Asan Cherkezov Department of Neuropathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Abigail K. Suwala Department of Neuropathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Tereza Lausová Department of Neuropathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Matija Snuderl Department of Pathology, New York University Langone Health and School of Medicine, New York, New York, USA
  • David Capper Department of Neuropathology, Charité - Universitätsmedizin Berlin, Berlin, Germany; German Cancer Consortium, Berlin, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Martin Sill Division of Pediatric Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
  • David T. W. Jones Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Pediatric Glioma Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany
  • Stefan M. Pfister Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany
  • Felix Sahm Department of Neuropathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
  • Andreas von Deimling Department of Neuropathology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany

DOI:

https://doi.org/10.17879/freeneuropathology-2024-5345

Keywords:

Glioblastoma, Copy Number Variations, CNV, Methylation, Classification, 7/10 signature, EGFR, CDKN2A/B, Amplification, Homozygous deletion

Abstract

The morphological patterns leading to the diagnosis of glioblastoma may also commonly be observed in several other distinct tumor entities, which can result in a mixed bag of tumors subsumed under this diagnosis. The 2021 WHO Classification of CNS Tumors has separated several of these entities from the diagnosis of glioblastoma, IDH-wildtype. This study determines the DNA methylation classes most likely receiving the diagnosis glioblastoma, IDH wildtype according to the definition by the WHO 2021 Classification and provides comparative copy number analyses.

We identified 10782 methylome datasets uploaded to the web page www.molecularneuropathology.org with a calibrated score of ≥0.9 by the Heidelberg Brain Tumor Classifier version v12.8. These methylation classes were characterized by the diagnosis glioblastoma being the most frequent classification encountered in each of the classes according to the WHO 2021 definition. Further, methylation classes selected for this study predominantly contained adult patients.

Unsupervised clustering confirmed the presence of nine methylation classes containing tumors most likely receiving the diagnosis glioblastoma, IDH-wildtype according to the WHO 2021 definition. Copy number analysis and a focus on genes with typical numerical alterations in glioblastoma revealed clear differences between the nine methylation classes. Although great progress in diagnostic precision has been achieved over the last decade, our data clearly demonstrate that glioblastoma, IDH-wildtype still is a heterogeneous group in need of further stratification.

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Published

2024-03-22

How to Cite

Reuss, D. E., Schrimpf , D., Cherkezov , A., Suwala , A. K., Lausová , T., Snuderl , M., Capper , D., Sill, M., Jones , D. T. W., Pfister , S. M., Sahm , F., & von Deimling, A. (2024). Heterogeneity of DNA methylation profiles and copy number alterations in 10782 adult-type glioblastomas, IDH-wildtype. Free Neuropathology, 5, 7. https://doi.org/10.17879/freeneuropathology-2024-5345

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Original Papers