Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT
Open accessAbstract
The "integrated diagnosis" for infiltrating gliomas in the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system requires assessment of the tumor for IDH mutations and 1p/19q codeletion. Since TERT promoter mutations and ATRX alterations have been shown to be associated with prognosis, we analyzed whether these tumor markers provide additional prognostic information within each of the five WHO 2016 categories. We used data for 1206 patients from the UCSF Adult Glioma Study, the Mayo Clinic and The Cancer Genome Atlas (TCGA) with infiltrative glioma, grades II-IV for whom tumor status for IDH, 1p/19q codeletion, ATRX, and TERT had been determined. All cases were assigned to one of 5 groups following the WHO 2016 diagnostic criteria based on their morphologic features, and IDH and 1p/19q codeletion status. These groups are: (1) Oligodendroglioma, IDH-mutant and 1p/19q-codeleted; (2) Astrocytoma, IDH-mutant; (3) Glioblastoma, IDH-mutant; (4) Glioblastoma, IDH-wildtype; and (5) Astrocytoma, IDH-wildtype. Within each group, we used univariate and multivariate Cox proportional hazards models to assess associations of overall survival with patient age at diagnosis, grade, and ATRX alteration status and/or TERT promoter mutation status. Among Group 1 IDH-mutant 1p/19q-codeleted oligodendrogliomas, the TERT-WT group had significantly worse overall survival than the TERT-MUT group (HR: 2.72, 95% CI 1.05-7.04, p = 0.04). In both Group 2, IDH-mutant astrocytomas and Group 3, IDH-mutant glioblastomas, neither TERT mutations nor ATRX alterations were significantly associated with survival. Among Group 4, IDH-wildtype glioblastomas, ATRX alterations were associated with favorable outcomes (HR: 0.36, 95% CI 0.17-0.81, p = 0.01). Among Group 5, IDH-wildtype astrocytomas, the TERT-WT group had significantly better overall survival than the TERT-MUT group (HR: 0.48, 95% CI 0.27-0.87), p = 0.02). Thus, we present evidence that in certain WHO 2016 diagnostic groups, testing for TERT promoter mutations or ATRX alterations may provide additional useful prognostic information.
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In adult HGG, ATRX loss associates with IDH mutations and TP53 loss and is associated with improved prognosis.
“Furthermore, in adult HGG, ATRX loss associates with IDH mutations and TP53 loss and is also associated with improved prognosis (Pekmezci et al., 2017; Wiestler et al., 2013), potentially due to better resection of focal tumors during surgery.”
From H3.3K27M Cooperates with Trp53 Loss and PDGFRA Gain in Mouse Embryonic Neural Progenitor Cells to Induce Invasive High-Grade Gliomas (2017) · cites this paper as Pekmezci et al., 2017
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- Authors
- Pekmezci, M., Rice, T., Molinaro, A. M., Walsh, K. M., Decker, P. A., Hansen, H., Sicotte, H., Kollmeyer, T. M., McCoy, L. S., Sarkar, G., Perry, A., Giannini, C., Tihan, T., Berger, M. S., Wiemels, J. L., Bracci, P. M., Eckel-Passow, J. E., Lachance, D. H., Clarke, J., Taylor, J. W., Luks, T., Wiencke, J. K., Jenkins, R. B., & Wrensch, M. R.
- Affiliations
- San Francisco VA Medical Center (US)
- University of California, San Francisco (US)
- Mayo Clinic (US)
- Corresponding author
- Pekmezci, Melike
- ORCID
- Pekmezci, Melike
- Molinaro, Annette M.
- Walsh, Kyle M.
- Decker, Paul A.
- Hansen, Helen
- Sicotte, Hugues
- Kollmeyer, Thomas M.
- McCoy, Lucie S.
- Sarkar, Gobinda
- Perry, Arie
- Giannini, Caterina
- Berger, Mitchel S.
- Wiemels, Joseph L.
- Bracci, Paige M.
- Lachance, Daniel H.
- Clarke, Jennifer
- Taylor, Jennie W.
- Luks, Tracy
- Wiencke, John K.
- Jenkins, Robert B.
- Wrensch, Margaret R.
- Venue
- Acta Neuropathologica
- Published
- 2017-03-02
- Volume
- 133
- Issue
- 6
- Pages
- 1001-1016
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC5432658
- OpenAlex
- W2593604059
- Cited by
- 319
- References
- 29
- Citations by year
- 2026: 8 · 2025: 27 · 2024: 15 · 2023: 33 · 2022: 38 · 2021: 52 · 2020: 50 · 2019: 37 · 2018: 43 · 2017: 14 · 2016: 1
- FWCI
- 22.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (R01CA52689)
- National Cancer Institute (P50CA097257, R01CA126831, R01CA139020, R25CA112355, P50CA108961, P30CA15083)
- National Institute of Neurological Disorders and Stroke (RC1NS068222Z)
- loglio Collective
- National Brain Tumor Foundation
- Sontag Foundation
- Bernie and Edith Waterman Foundation
- Ting Tsung and Wei Fong Chao Family Foundation
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- infiltrating glioma, TERT promoter mutation, prognostic factors, overall survival, IDH mutation, 1p/19q codeletion, glioblastoma, astrocytoma, oligodendroglioma, adult glioma, age at diagnosis, tumor grade
- MeSH terms
- X-linked Nuclear Protein, Adolescent, Adult, Aged, Aged, 80 and over, Female, Glioma, Humans, Isocitrate Dehydrogenase, Male, Middle Aged, Mutation, Prognosis, Biomarkers, Tumor, World Health Organization, Case-Control Studies, Central Nervous System Neoplasms, Telomerase, Kaplan-Meier Estimate, Young Adult, Neoplasm Grading
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