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

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

Fingerprint

Neurilemmoma
Meta-Analysis
Incidence
Histones
Lysine
Cohort Studies
Databases
Guidelines
Radiation

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

H3K27 trimethylation loss in malignant peripheral nerve sheath tumor : a systematic review and meta-analysis with diagnostic implications. / Lu, Victor M.; Marek, Tomas; Gilder, Hannah E.; Puffer, Ross C.; Raghunathan, Aditya; Spinner, Robert J.; Daniels, David.

In: Journal of neuro-oncology, 01.01.2019.

Research output: Contribution to journalReview article

@article{896582d3c67d4023b43c3b724a6518b5,
title = "H3K27 trimethylation loss in malignant peripheral nerve sheath tumor: a systematic review and meta-analysis with diagnostic implications",
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.",
keywords = "H3K27me3, Lysine, Malignant peripheral nerve sheath tumor, MPNST, Sensitivity, Trimethylation",
author = "Lu, {Victor M.} and Tomas Marek and Gilder, {Hannah E.} and Puffer, {Ross C.} and Aditya Raghunathan and Spinner, {Robert J.} and David Daniels",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s11060-019-03247-3",
language = "English (US)",
journal = "Journal of Neuro-Oncology",
issn = "0167-594X",
publisher = "Kluwer Academic Publishers",

}

TY - JOUR

T1 - H3K27 trimethylation loss in malignant peripheral nerve sheath tumor

T2 - a systematic review and meta-analysis with diagnostic implications

AU - Lu, Victor M.

AU - Marek, Tomas

AU - Gilder, Hannah E.

AU - Puffer, Ross C.

AU - Raghunathan, Aditya

AU - Spinner, Robert J.

AU - Daniels, David

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - H3K27me3

KW - Lysine

KW - Malignant peripheral nerve sheath tumor

KW - MPNST

KW - Sensitivity

KW - Trimethylation

UR - http://www.scopus.com/inward/record.url?scp=85069699273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069699273&partnerID=8YFLogxK

U2 - 10.1007/s11060-019-03247-3

DO - 10.1007/s11060-019-03247-3

M3 - Review article

JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

SN - 0167-594X

ER -