TP53, ATRX alterations, and low tumor mutation load feature IDH-wildtype giant cell glioblastoma despite exceptional ultra-mutated tumors.

ATRX TP53 giant cell glioblastoma next-generation sequencing tumor mutation load

Journal

Neuro-oncology advances
ISSN: 2632-2498
Titre abrégé: Neurooncol Adv
Pays: England
ID NLM: 101755003

Informations de publication

Date de publication:
Historique:
entrez: 10 7 2020
pubmed: 10 7 2020
medline: 10 7 2020
Statut: epublish

Résumé

Giant cell glioblastoma (gcGBM) is a rare morphological variant of IDH-wildtype (IDHwt) GBM that occurs in young adults and have a slightly better prognosis than "classic" IDHwt GBM. We studied 36 GBMs, 14 with a histopathological diagnosis of gcGBM and 22 with a giant cell component. We analyzed the genetic profile of the most frequently mutated genes in gliomas and assessed the tumor mutation load (TML) by gene-targeted next-generation sequencing. We validated our findings using The Cancer Genome Atlas (TCGA) data. p53 was altered by gene mutation or protein overexpression in all cases, while driver gcGBMs have molecular features that contrast to "classic" IDHwt GBMs: unusually frequent

Sections du résumé

BACKGROUND BACKGROUND
Giant cell glioblastoma (gcGBM) is a rare morphological variant of IDH-wildtype (IDHwt) GBM that occurs in young adults and have a slightly better prognosis than "classic" IDHwt GBM.
METHODS METHODS
We studied 36 GBMs, 14 with a histopathological diagnosis of gcGBM and 22 with a giant cell component. We analyzed the genetic profile of the most frequently mutated genes in gliomas and assessed the tumor mutation load (TML) by gene-targeted next-generation sequencing. We validated our findings using The Cancer Genome Atlas (TCGA) data.
RESULTS RESULTS
p53 was altered by gene mutation or protein overexpression in all cases, while driver
CONCLUSIONS CONCLUSIONS
gcGBMs have molecular features that contrast to "classic" IDHwt GBMs: unusually frequent

Identifiants

pubmed: 32642724
doi: 10.1093/noajnl/vdz059
pii: vdz059
pmc: PMC7212869
doi:

Types de publication

Journal Article

Langues

eng

Pagination

vdz059

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

Références

J Neuropathol Exp Neurol. 2015 Mar;74(3):241-9
pubmed: 25668564
Cancer Res. 2018 Jun 1;78(11):2966-2977
pubmed: 29545335
Lab Invest. 1999 Feb;79(2):123-9
pubmed: 10068201
J Clin Neurosci. 2014 Dec;21(12):2129-34
pubmed: 25037316
J Neurooncol. 2014 May;118(1):131-9
pubmed: 24590827
Cold Spring Harb Perspect Med. 2016 Jun 01;6(6):
pubmed: 27252396
Brain Pathol. 2016 Jul;26(4):517-22
pubmed: 26443480
J Neurosurg. 2004 Aug;101(2):219-26
pubmed: 15309911
Brain Pathol. 2019 Nov;29(6):782-792
pubmed: 30861589
Transl Lung Cancer Res. 2018 Dec;7(6):616-630
pubmed: 30505706
J Neurooncol. 2015 May;122(3):441-50
pubmed: 25682093
Brain Tumor Pathol. 2015 Jan;32(1):22-30
pubmed: 24748374
J Neuropathol Exp Neurol. 2018 Aug 1;77(8):710-716
pubmed: 30010995
Am J Pathol. 1997 Sep;151(3):853-7
pubmed: 9284834
Genes Cancer. 2011 Apr;2(4):466-74
pubmed: 21779514
Neuro Oncol. 2016 Oct 1;18(suppl_5):v1-v75
pubmed: 28475809
Mol Oncol. 2011 Aug;5(4):315-23
pubmed: 21852209
Brain Pathol. 2015 May;25(3):256-65
pubmed: 25040820
Neuro Oncol. 2009 Dec;11(6):833-41
pubmed: 19332771
Cancer Genet Cytogenet. 2007 May;175(1):26-34
pubmed: 17498554
J Clin Neurosci. 2014 Oct;21(10):1709-13
pubmed: 24980627
Neuro Oncol. 2015 Oct;17(10):1356-64
pubmed: 25740784
BMC Bioinformatics. 2011 Nov 21;12:451
pubmed: 22099972
Cancer Discov. 2016 Nov;6(11):1230-1236
pubmed: 27683556
Science. 2011 Jul 22;333(6041):425
pubmed: 21719641
Cancer Res. 2006 Apr 15;66(8):3987-91
pubmed: 16618716
Cancers (Basel). 2019 Jun 04;11(6):
pubmed: 31167453
Cell. 2018 Apr 5;173(2):291-304.e6
pubmed: 29625048
Am J Clin Pathol. 2009 Feb;131(2):257-63
pubmed: 19141386

Auteurs

Diana Cantero (D)

Department of Pathology (Neuropathology) and Instituto de Investigación i+12, Hospital Universitario 12 de Octubre, Madrid, Spain.

Manuela Mollejo (M)

Department of Pathology, Virgen de la Salud Hospital, Toledo, Spain.

Juan M Sepúlveda (JM)

Department of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain.

Nicky D'Haene (N)

Department of Pathology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Myriam J Gutiérrez-Guamán (MJ)

Department of Pathology (Neuropathology) and Instituto de Investigación i+12, Hospital Universitario 12 de Octubre, Madrid, Spain.

Ángel Rodríguez de Lope (Á)

Department of Neurosurgery, Virgen de la Salud Hospital, Toledo, Spain.

Concepción Fiaño (C)

Department of Pathology, Alvaro Cunqueiro Hospital, Vigo, Spain.

Javier S Castresana (JS)

Department of Biochemistry and Genetics, University of Navarra School of Sciences, Pamplona, Spain.

Laetitia Lebrun (L)

Department of Pathology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Juan A Rey (JA)

IdiPaz Research Unit, La Paz University Hospital, Madrid, Spain.

Isabelle Salmon (I)

Department of Pathology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Bárbara Meléndez (B)

Department of Pathology, Virgen de la Salud Hospital, Toledo, Spain.
Department of Pathology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Aurelio Hernández-Laín (A)

Department of Pathology (Neuropathology) and Instituto de Investigación i+12, Hospital Universitario 12 de Octubre, Madrid, Spain.

Classifications MeSH