AI Article Synopsis
- IDH mutant astrocytomas have traditionally been graded based on their morphology, but recent guidelines now include the homozygous deletion of CDKN2A/B as a key biomarker for grade 4 tumors.
- A study of 98 cases revealed that while traditional histological grading did not significantly predict patient outcomes, stratification by the CDKN2A/B deletion or DNA methylation subclass did show significant differences in overall survival (OS).
- The findings suggest that current WHO grading for these tumors has limited prognostic value, while DNA methylation classification could lead to improved predictions for patient outcomes.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11145445 | PMC |
| http://dx.doi.org/10.1093/neuonc/noae009 | DOI Listing |
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