Malignant Peripheral Nerve Sheath Tumor (MPNST)

Overview

Malignant peripheral nerve sheath tumor (MPNST) is a malignant neoplasm of nerve sheath origin, classified under nerve sheath tumors (parent: NST) in the OncoTree hierarchy. MPNST can arise sporadically, in the setting of neurofibromatosis type 1 (NF1), or as a radiation-associated sarcoma.

Cohorts in the corpus

Recurrent alterations

  • NF1 inactivation in MPNST (and GIST) was established prior to 2010; Barretina et al. confirmed this as background when reporting novel somatic NF1 alterations in MFS and PLLS as “the first report outside MPNST/GIST.” PMID:20601955
  • CDKN2A/CDKN2B deletions in 92% of RT-MPNST vs 44% of sporadic MPNST PMID:37350195.
  • NF1 inactivating mutations/deletions in 67% of RT-MPNST vs 36% sporadic PMID:37350195.
  • TEK deletions in 42% of RT-MPNST vs 6% sporadic PMID:37350195.
  • SUZ12 inactivating mutations/deletions (PRC2 complex component) in 33% of RT-MPNST vs 17% sporadic PMID:37350195.
  • TP53 LOF mutations/deletions in 25% of RT-MPNST PMID:37350195.
  • PTPRD mutations/deletions in 25% of RT-MPNST vs 5% sporadic PMID:37350195.
  • RT-MPNST had the highest fraction of genome altered (FGA, 51%) among all RT-sarcoma histotypes; significantly higher than sporadic MPNST (31%, P = 0.014) PMID:37350195.
  • RT-MPNST was enriched for genome-wide arm-level copy number changes PMID:37350195.
  • PRC2 core subunits EED or SUZ12 are inactivated in 92% of sporadic, 70% of NF1-associated, and 90% of radiotherapy-associated MPNSTs; NF1 (82%), CDKN2A (81%), and TP53 (42%) co-occur; H3K27me3 IHC tracks PRC2 loss and distinguishes MPNST from benign neurofibroma PMID:25240281
  • MPNST (n=5) was underpowered for deep subtype analysis; APOBEC mutational signatures (COSMIC2/13) were modestly elevated in MPNST (alongside DDLPS) vs other sarcoma histologies (p<10⁻⁶, Kruskal-Wallis), and the cohort was included in pan-sarcoma SMG analysis identifying TP53, ATRX, and RB1 as recurrently mutated PMID:29100075

Subtypes

  • Radiation-associated MPNST (RT-MPNST): Distinguished by near-universal CDKN2A/B deletions (92%), high NF1 inactivation (67%), and the highest FGA among RT-sarcomas. Median latency from radiation to diagnosis: 12.5 years PMID:37350195.
  • Sporadic MPNST: Lower rates of CDKN2A/B deletion (44%), NF1 inactivation (36%), and lower FGA (31%) PMID:37350195.

Therapeutic landscape

  • Investigations on small molecular inhibitors of DNA methyltransferase (DNMT1) are ongoing in sporadic/NF1-related and RT-MPNSTs harboring PRC2-inactivating mutations (e.g., SUZ12) PMID:37350195.

Sources

  • PMID:37350195 — Dermawan JK et al., J Pathol 2023. Comparative genomic analysis of 82 RT-sarcomas including 12 RT-MPNSTs.
  • PMID:20601955 — Barretina et al. Nature 2010. Integrative genomic analysis of 207 high-grade soft tissue sarcomas (NF1 in MPNST cited as prior established biology).

This page was processed by crosslinker on 2026-05-04. - PMID:25240281

This page was processed by wiki-cli on 2026-05-12. - PMID:29100075

This page was processed by wiki-cli on 2026-05-15.