Total copy number variation as a prognostic factor in adult astrocytoma subtypes

Kanish Mirchia, Adwait Amod Sathe, Jamie M. Walker, Yelena Fudym, Kristyn Galbraith, Mariano S. Viapiano, Robert J. Corona, Matija Snuderl, Chao Xing, Kimmo J Hatanpaa, Timothy E. Richardson

Research output: Contribution to journalArticle

Abstract

Since the discovery that IDH1/2 mutations confer a significantly better prognosis in astrocytomas, much work has been done to identify other molecular signatures to help further stratify lower-grade astrocytomas and glioblastomas, with the goal of accurately predicting clinical outcome and identifying potentially targetable mutations. In the present study, we subclassify 135 astrocytomas (67 IDH-wildtype and 68 IDH-mutant) from The Cancer Genome Atlas dataset (TCGA) on the basis of grade, IDH-status, and the previously established prognostic factors, CDK4 amplification and CDKN2A/B deletion, within the IDH-mutant groups. We analyzed these groups for total copy number variation (CNV), total mutation burden, chromothripsis, specific mutations, and amplifications/deletions of specific genes/chromosomal regions. Herein, we demonstrate that across all of these tumor groups, total CNV level is a relatively consistent prognostic factor. We also identified a trend towards increased levels of chromothripsis in tumors with lower progression-free survival (PFS) and overall survival (OS) intervals. While no significant differences were identified in overall mutation load, we did identify a significantly higher number of cases with mutations in genes with functions related to maintaining genomic stability in groups with higher mean CNV and worse PFS and OS intervals, particularly in the IDH-mutant groups. Our data further support the case for total CNV level as a potential prognostic factor in astrocytomas, and suggest mutations in genes responsible for overall genomic instability as a possible underlying mechanism for some astrocytomas with poor clinical outcome.

Original languageEnglish (US)
Number of pages1
JournalActa neuropathologica communications
Volume7
Issue number1
DOIs
StatePublished - Jun 10 2019

Fingerprint

Astrocytoma
Mutation
Genomic Instability
Disease-Free Survival
Neoplasms
Atlases
Sequence Deletion
Gene Deletion
Glioblastoma
Genes
Genome

Keywords

  • Astrocytoma
  • CNV
  • Copy number variation
  • GBM
  • Glioblastoma
  • Glioma
  • TCGA

ASJC Scopus subject areas

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

Cite this

Mirchia, K., Sathe, A. A., Walker, J. M., Fudym, Y., Galbraith, K., Viapiano, M. S., ... Richardson, T. E. (2019). Total copy number variation as a prognostic factor in adult astrocytoma subtypes. Acta neuropathologica communications, 7(1). https://doi.org/10.1186/s40478-019-0746-y

Total copy number variation as a prognostic factor in adult astrocytoma subtypes. / Mirchia, Kanish; Sathe, Adwait Amod; Walker, Jamie M.; Fudym, Yelena; Galbraith, Kristyn; Viapiano, Mariano S.; Corona, Robert J.; Snuderl, Matija; Xing, Chao; Hatanpaa, Kimmo J; Richardson, Timothy E.

In: Acta neuropathologica communications, Vol. 7, No. 1, 10.06.2019.

Research output: Contribution to journalArticle

Mirchia, K, Sathe, AA, Walker, JM, Fudym, Y, Galbraith, K, Viapiano, MS, Corona, RJ, Snuderl, M, Xing, C, Hatanpaa, KJ & Richardson, TE 2019, 'Total copy number variation as a prognostic factor in adult astrocytoma subtypes', Acta neuropathologica communications, vol. 7, no. 1. https://doi.org/10.1186/s40478-019-0746-y
Mirchia, Kanish ; Sathe, Adwait Amod ; Walker, Jamie M. ; Fudym, Yelena ; Galbraith, Kristyn ; Viapiano, Mariano S. ; Corona, Robert J. ; Snuderl, Matija ; Xing, Chao ; Hatanpaa, Kimmo J ; Richardson, Timothy E. / Total copy number variation as a prognostic factor in adult astrocytoma subtypes. In: Acta neuropathologica communications. 2019 ; Vol. 7, No. 1.
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