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

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 w...

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Bibliographic Details
Published in:Journal of neuro-oncology 2019-09, Vol.144 (3), p.433-443
Main Authors: Lu, Victor M., Marek, Tomas, Gilder, Hannah E., Puffer, Ross C., Raghunathan, Aditya, Spinner, Robert J., Daniels, David J.
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - genetics
DNA Methylation
Histones - genetics
Humans
Lysine
Medicine
Medicine & Public Health
Meta-analysis
Methylation
Neurofibrosarcoma - diagnosis
Neurofibrosarcoma - genetics
Neurology
Oncology
Peripheral nerves
Prognosis
Systematic review
Topic Review
Tumors
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Summary: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.
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-019-03247-3