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Acta Neuropathol. 2017 Jun;133(6):1001-1016. doi: 10.1007/s00401-017-1690-1. Epub 2017 Mar 2.

Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT.

Author information

1
Department of Pathology, University of California, Box 0102, 505 Parnassus Avenue, Room M-551, San Francisco, CA, 94143, USA. melike.pekmezci@ucsf.edu.
2
Department of Anatomic Pathology, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA. melike.pekmezci@ucsf.edu.
3
Department of Neurological Surgery, University of California, San Francisco, CA, USA.
4
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
5
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
6
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
7
Department of Pathology, University of California, Box 0102, 505 Parnassus Avenue, Room M-551, San Francisco, CA, 94143, USA.
8
Department of Radiology, University of California, San Francisco, CA, USA.
9
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
10
Institute of Human Genetics, University of California, San Francisco, CA, USA.

Abstract

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.

KEYWORDS:

ATRX alteration; Brain tumor prognosis; Glioma classification; TERT promoter mutation; Telomere maintenance

PMID:
28255664
PMCID:
PMC5432658
DOI:
10.1007/s00401-017-1690-1
[Indexed for MEDLINE]
Free PMC Article

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