Prognostic value of DNA methylation subclassification, aneuploidy, and CDKN2A/B homozygous deletion in predicting clinical outcome of IDH mutant astrocytomas

Kristyn Galbraith, Mekka Garcia, Siyu Wei, Anna Chen, Chanel Schroff, Jonathan Serrano, Donato Pacione, Dimitris G. Placantonakis, Christopher M. William, Arline Faustin, David Zagzag, Marissa Barbaro, Maria Del Pilar Guillermo Prieto Eibl, Mitsuaki Shirahata, David Reuss, Quynh T. Tran, Zahangir Alom, Andreas von Deimling, Brent A. Orr, Erik P. SulmanJohn G. Golfinos, Daniel A. Orringer, Rajan Jain, Evan Lieberman, Yang Feng, Matija Snuderl

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology. The 5th edition of the Central Nervous System World Health Organization (WHO) introduces CDKN2A/B homozygous deletion as a biomarker of grade 4. We sought to investigate the prognostic impact of DNA methylation-derived molecular biomarkers for IDH mutant astrocytoma. Methods. We analyzed 98 IDH mutant astrocytomas diagnosed at NYU Langone Health between 2014 and 2022. We reviewed DNA methylation subclass, CDKN2A/B homozygous deletion, and ploidy and correlated molecular biomarkers with histological grade, progression free (PFS), and overall (OS) survival. Findings were confirmed using 2 independent validation cohorts. Results. There was no significant difference in OS or PFS when stratified by histologic WHO grade alone, copy number complexity, or extent of resection. OS was significantly different when patients were stratified either by CDKN2A/B homozygous deletion or by DNA methylation subclass (P value = .0286 and .0016, respectively). None of the molecular biomarkers were associated with significantly better PFS, although DNA methylation classification showed a trend (P value = .0534). Conclusions. The current WHO recognized grading criteria for IDH mutant astrocytomas show limited prognostic value. Stratification based on DNA methylation shows superior prognostic value for OS.

Original languageEnglish (US)
Pages (from-to)1042-1051
Number of pages10
JournalNeuro-Oncology
Volume26
Issue number6
DOIs
StatePublished - Jun 1 2024

Keywords

  • DNA methylation
  • grading
  • IDH mutant astrocytoma
  • molecular
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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