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Malignant Peripheral Nerve Sheath Tumor

Malignant Peripheral Nerve Sheath Tumor Research Notes

Manual MONDO:0017827

Malignant Peripheral Nerve Sheath Tumor Research Notes

Date: 2026-04-12

Modeling choices

This curation explicitly follows the cancer-modeling guidance called out from dismech issue #1198.

  • The dismech page is the disease-level mechanism graph for MPNST as a whole, not a page-per-ontology-subclass expansion.
  • disease_term is MONDO-first: MONDO:0017827 malignant peripheral nerve sheath tumor.
  • NCIT was handled where the current schema is strongest today: NCIT:C3798 is recorded in the disease-level notes as the requested disease cross-reference, and NCIT histopathology grounding was used for NCIT:C53643 Spindle Cell Pattern.
  • Subtypes were modeled as flat facet axes, not as separate dismech diseases: predisposition context (NF1-Associated, Sporadic, Radiation-Associated) and histology (Epithelioid, Malignant Triton Tumor).
  • Epithelioid remained inside the parent MPNST page even though it has a subtype-specific SMARCB1 branch, because the broader disease still shares a common MPNST clinical/pathologic frame and the schema can represent the distinct mechanism with subtype-scoped nodes.

Ontology grounding used

  • Disease: MONDO:0017827 malignant peripheral nerve sheath tumor
  • Histologic subtype: MONDO:0004540 epithelioid malignant peripheral nerve sheath tumor
  • Histologic subtype: MONDO:0016757 malignant triton tumor
  • Histopathology: NCIT:C53643 Spindle Cell Pattern
  • Cell type: CL:0002573 Schwann cell
  • Key GO processes:
  • GO:0007265 Ras protein signal transduction
  • GO:0000075 cell cycle checkpoint signaling
  • GO:0006974 DNA damage response
  • GO:0006325 chromatin organization
  • GO:0010468 regulation of gene expression
  • GO:0008283 cell population proliferation
  • Phenotypes:
  • HP:0031459 Soft tissue neoplasm
  • HP:0012531 Pain
  • HP:0001324 Muscle weakness
  • Treatments:
  • MAXO:0000004 surgical procedure
  • MAXO:0000014 radiation therapy
  • MAXO:0000647 chemotherapy
  • CHEBI:5864 ifosfamide

Core literature used in the YAML

Disease definition and subtype context

  • PMID:24470531 Farid et al. 2014 review
  • Used for disease definition, NF1/sporadic/radiation-associated subtype framing, and poor-prognosis treatment context.

  • Key quote used: "In 50% of cases, they occur in the context of neurofibromatosis type I ... the remainder arise sporadically or following radiation therapy."

  • PMID:38954182 Somaiah et al. 2024 review

  • Used for current overview of anatomy, spindle-cell identity, surgical role, and the absence of a targeted standard of care.

Core conventional MPNST mechanism

  • PMID:36598417 Cortes-Ciriano et al. 2023
  • Key evolutionary paper for ordering events: NF1 biallelic loss -> CDKN2A/TP53 +/- PRC2 loss -> extensive SCNAs.

  • Also supports the H3K27me3-loss branch as a distinct evolutionary path.

  • PMID:29118384 Brohl et al. 2017

  • Used for recurrent NF1, SUZ12, EED, TP53, and CDKN2A lesions and for convergent Ras-pathway activation.

  • PMID:30722027 Pemov et al. 2019

  • Used to keep the progression model atomic: CDKN2A/B deletion is an early step in PN -> atypical neurofibroma transition, whereas PRC2 loss is later.

  • PMID:25240281 Lee et al. 2014

  • Key PRC2 paper used for:
    • recurrent SUZ12 / EED inactivation across etiologies
    • H3K27me3 loss
    • homeobox/developmental gene derepression
    • cell-growth rescue after PRC2 restoration

Diagnostic biomarker / pathology

  • PMID:26645727 Prieto-Granada et al. 2016

  • Used for H3K27me3-loss diagnostic performance and the fact that epithelioid tumors retain H3K27me3.

  • PMID:31175328 Marchione et al. 2019

  • Used for the more specific H3K27me2-loss biomarker.

Histologic subtype-specific biology

  • PMID:25602794 Jo and Fletcher 2015

  • Used for epithelioid subtype morphology, superficial distribution, diffuse S100 positivity, and infrequent NF1 association.

  • PMID:30864974 Schaefer et al. 2019

  • Used for subtype-scoped SMARCB1 inactivation in epithelioid MPNST.

  • PMID:17149968 Stasik and Tawfik 2006

  • Used for malignant triton tumor as the rhabdomyoblastic differentiation facet of MPNST.

Clinical phenotype and treatment

  • PMID:36752552 Donaldson et al. 2023

  • Used for enlarging mass, pain, and motor/sensory deficit presentation.

  • PMID:16033085 Friedrich et al. 2005

  • Used for NF1 surveillance language around atypical pain, tumor growth, and neurologic deficits as malignant-warning features.

  • PMID:27281262 Bishop et al. 2018

  • Used for combined surgery plus radiotherapy and local-control outcomes.

  • PMID:40795877 Jansma et al. 2025

  • Used to refine radiotherapy interpretation: lower local-recurrence risk in sporadic disease, unclear benefit in NF1-associated disease.

  • PMID:28546782 Hirbe et al. 2017

  • Used for direct human evidence that ifosfamide/anthracycline-based chemotherapy can induce response.

Curation-specific decisions

  • I did not split epithelioid MPNST into its own disease file even though it has a distinct SMARCB1 branch. Under the #1198 rule set, that would only be warranted if it needed a genuinely separate disease-level mechanism graph. Here, subtype-scoped mechanism and genetic nodes are sufficient.
  • I did not create separate files for NF1-associated or radiation-associated MPNST. Those are important subtype facets, but they still sit inside the same parent MPNST mechanism graph.
  • I kept the conventional pathophysiology nodes atomic: NF1 Biallelic Inactivation, Ras Pathway Hyperactivation, CDKN2A/B Loss, TP53 Pathway Loss, PRC2 Core Complex Inactivation, H3K27 Trimethylation Loss, Developmental Gene Derepression, and Copy-Number Driven Genomic Instability.