Adult infiltrating gliomas with WHO 2016 integrated diagnosis

additional prognostic roles of ATRX and TERT

Melike Pekmezci, Terri Rice, Annette M. Molinaro, Kyle M. Walsh, Paul A. Decker, Helen Hansen, Hugues Sicotte, Thomas M. Kollmeyer, Lucie S. McCoy, Gobinda Sarkar, Arie Perry, Caterina Giannini, Tarik Tihan, Mitchel S. Berger, Joseph L. Wiemels, Paige M. Bracci, Jeanette E Eckel-Passow, Daniel H Lachance, Jennifer Clarke, Jennie W. Taylor & 4 others Tracy Luks, John K. Wiencke, Robert Brian Jenkins, Margaret R. Wrensch

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalActa Neuropathologica
DOIs
StateAccepted/In press - Mar 2 2017

Fingerprint

Glioma
Astrocytoma
Glioblastoma
Mutation
Oligodendroglioma
Survival
Central Nervous System Neoplasms
Neoplasms
Atlases
Tumor Biomarkers
Proportional Hazards Models
Genome

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Pekmezci, M., Rice, T., Molinaro, A. M., Walsh, K. M., Decker, P. A., Hansen, H., ... Wrensch, M. R. (Accepted/In press). Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT. Acta Neuropathologica, 1-16. https://doi.org/10.1007/s00401-017-1690-1

Adult infiltrating gliomas with WHO 2016 integrated diagnosis : additional prognostic roles of ATRX and TERT. / Pekmezci, Melike; Rice, Terri; 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; Tihan, Tarik; Berger, Mitchel S.; Wiemels, Joseph L.; Bracci, Paige M.; Eckel-Passow, Jeanette E; Lachance, Daniel H; Clarke, Jennifer; Taylor, Jennie W.; Luks, Tracy; Wiencke, John K.; Jenkins, Robert Brian; Wrensch, Margaret R.

In: Acta Neuropathologica, 02.03.2017, p. 1-16.

Research output: Contribution to journalArticle

Pekmezci, M, Rice, T, Molinaro, AM, Walsh, KM, Decker, PA, Hansen, H, Sicotte, H, Kollmeyer, TM, McCoy, LS, Sarkar, G, Perry, A, Giannini, C, Tihan, T, Berger, MS, Wiemels, JL, Bracci, PM, Eckel-Passow, JE, Lachance, DH, Clarke, J, Taylor, JW, Luks, T, Wiencke, JK, Jenkins, RB & Wrensch, MR 2017, 'Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT', Acta Neuropathologica, pp. 1-16. https://doi.org/10.1007/s00401-017-1690-1
Pekmezci, Melike ; Rice, Terri ; 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 ; Tihan, Tarik ; Berger, Mitchel S. ; Wiemels, Joseph L. ; Bracci, Paige M. ; Eckel-Passow, Jeanette E ; Lachance, Daniel H ; Clarke, Jennifer ; Taylor, Jennie W. ; Luks, Tracy ; Wiencke, John K. ; Jenkins, Robert Brian ; Wrensch, Margaret R. / Adult infiltrating gliomas with WHO 2016 integrated diagnosis : additional prognostic roles of ATRX and TERT. In: Acta Neuropathologica. 2017 ; pp. 1-16.
@article{c38fbf4e60ff4525a4a237e557226c51,
title = "Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT",
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, Telomere maintenance, TERT promoter mutation",
author = "Melike Pekmezci and Terri Rice and Molinaro, {Annette M.} and Walsh, {Kyle M.} and Decker, {Paul A.} and Helen Hansen and Hugues Sicotte and Kollmeyer, {Thomas M.} and McCoy, {Lucie S.} and Gobinda Sarkar and Arie Perry and Caterina Giannini and Tarik Tihan and Berger, {Mitchel S.} and Wiemels, {Joseph L.} and Bracci, {Paige M.} and Eckel-Passow, {Jeanette E} and Lachance, {Daniel H} and Jennifer Clarke and Taylor, {Jennie W.} and Tracy Luks and Wiencke, {John K.} and Jenkins, {Robert Brian} and Wrensch, {Margaret R.}",
year = "2017",
month = "3",
day = "2",
doi = "10.1007/s00401-017-1690-1",
language = "English (US)",
pages = "1--16",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Adult infiltrating gliomas with WHO 2016 integrated diagnosis

T2 - additional prognostic roles of ATRX and TERT

AU - Pekmezci, Melike

AU - Rice, Terri

AU - Molinaro, Annette M.

AU - Walsh, Kyle M.

AU - Decker, Paul A.

AU - Hansen, Helen

AU - Sicotte, Hugues

AU - Kollmeyer, Thomas M.

AU - McCoy, Lucie S.

AU - Sarkar, Gobinda

AU - Perry, Arie

AU - Giannini, Caterina

AU - Tihan, Tarik

AU - Berger, Mitchel S.

AU - Wiemels, Joseph L.

AU - Bracci, Paige M.

AU - Eckel-Passow, Jeanette E

AU - Lachance, Daniel H

AU - Clarke, Jennifer

AU - Taylor, Jennie W.

AU - Luks, Tracy

AU - Wiencke, John K.

AU - Jenkins, Robert Brian

AU - Wrensch, Margaret R.

PY - 2017/3/2

Y1 - 2017/3/2

N2 - 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.

AB - 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.

KW - ATRX alteration

KW - Brain tumor prognosis

KW - Glioma classification

KW - Telomere maintenance

KW - TERT promoter mutation

UR - http://www.scopus.com/inward/record.url?scp=85014091994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014091994&partnerID=8YFLogxK

U2 - 10.1007/s00401-017-1690-1

DO - 10.1007/s00401-017-1690-1

M3 - Article

SP - 1

EP - 16

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

ER -