H3K27 trimethylation loss in malignant peripheral nerve sheath tumor: a systematic review and meta-analysis with diagnostic implications

Victor M. Lu, Tomas Marek, Hannah E. Gilder, Ross C. Puffer, Aditya Raghunathan, Robert J. Spinner, David Daniels

Research output: Contribution to journalReview article

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Abstract

Background: Multiple studies have reported the loss of trimethylation at lysine (K) 27 on histone 3 (H3K27me3) in high-grade malignant peripheral nerve sheath tumors (MPNSTs). However, the diagnostic potential of this finding in MPNSTs remains yet to be fully substantiated. Correspondingly, our aim was to pool systematically-identified metadata in the literature and substantiate the incidence of H3K27me3 loss in this setting. Methods: Searches of 7 electronic databases from inception to May 2019 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. The incidence of loss was then pooled by random-effects meta-analysis of proportions. Results: Nine pertinent studies described a total of 823 high-grade MPNST samples. When pooled, incidence (sensitivity) of complete H3K27me3 loss was estimated to be 53% (95% CI 42–64%). For MPNST subtypes, estimated incidences of complete loss in NF1 subtype was 52% (95% CI 41–62), in sporadic subtype was 53% (95% CI 36–70%), in the epithelioid subtype was 0% (95% CI 0–7%), and radiation-associated subtype was 98% (95% CI 86–100%). Finally, incidence of incomplete loss (specificity) in 1231 MPNST-mimic samples was estimated to be 96% (95% CI 90–99%). Certainty of these outcomes ranged from very low to high. Conclusions: The incidence of complete H3K27me3 loss is substantial in high-grade MPNSTs and is low in MPNST-mimics. Greater cohort study and biological investigation will validate the certainty of these findings as well as elucidate their true molecular and clinical significances.

Original languageEnglish (US)
JournalJournal of neuro-oncology
DOIs
StatePublished - Jan 1 2019

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Keywords

  • H3K27me3
  • Lysine
  • Malignant peripheral nerve sheath tumor
  • MPNST
  • Sensitivity
  • Trimethylation

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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