Myxofibrosarcoma (MFS)

Overview

Myxofibrosarcoma (formerly myxoid malignant fibrous histiocytoma) is a soft-tissue sarcoma of fibroblastic differentiation with prominent myxoid stroma, classified under Soft Tissue Sarcoma in OncoTree (parent: SOFT_TISSUE). It predominantly affects elderly patients, arises in the extremities, and has a high local recurrence rate.

Cohorts in the corpus

  • sarc_mskcc: 38 MFS patients (18.4% of 207 high-grade STS, including pleomorphic MFH), profiled by targeted resequencing (722 genes), 250K SNP-array SCNA, LOH, and expression arrays. PMID:20601955
  • sarcoma_ucla_2024: represented in the 24-subtype UCLA sarcoma PDTO biobank (194 specimens from 126 patients, Feb 2018–May 2022). PMID:39305899

Recurrent alterations

  • NF1 — mutated in 10.5% of MFS (point mutations + genomic deletions); biallelic inactivation (heterozygous mutation + WT-allele deletion) observed; loss linked to mTOR pathway activation. Two mutations (R304, Q369) previously reported as germline NF1 alleles. First report of somatic NF1 alterations outside MPNST/GIST. PMID:20601955
  • ERBB4 — mutations found on resequencing of MFS (and PLLS) samples. PMID:20601955
  • Complex karyotype: MFS clusters with DDLS, PLLS, and LMS as complex-karyotype subtypes with copy-neutral LOH; MFS and PLLS are strikingly similar genomically, supporting a unified molecular class. PMID:20601955
  • No recurrent driver alterations specifically characterized for MFS in the UCLA PDTO study. Complex karyotype with TP53 and RB1 alterations are common in the broader literature.
  • MFS (n=17) was molecularly indistinguishable from UPS across platforms; myxoid-stroma gene expression was the primary separator; recurrent CCNE1 (10%), VGLL3 (11%), and YAP1 (3%) amplifications implicate the Hippo pathway; high NK-cell and dendritic-cell immune signatures correlated with improved DSS, nominating MFS alongside UPS for checkpoint-inhibitor trials PMID:29100075

Subtypes

  • Graded I–III by degree of cellularity and mitotic activity (FNCLCC system).

Therapeutic landscape

  • mTOR inhibition proposed for NF1-deficient MFS: NF1 loss activates the RAS–mTOR axis. PMID:20601955
  • Patient-derived tumor organoid (PDTO) drug screening was applied across all 24 sarcoma subtypes in the UCLA cohort, including MFS. Across the full cohort, 80.4% of specimens screened had at least one significant drug response, and 59% had at least one FDA-approved or NCCN-recommended top-five regimen. PMID:39305899

Sources

  • PMID:20601955 — Barretina et al. Nature 2010. Integrative genomic analysis of 207 high-grade soft tissue sarcomas across seven subtypes (MSKCC Sarcoma Genome Project).
  • PMID:39305899 — Al Shihabi et al. Cell Stem Cell 2024. UCLA sarcoma PDTO drug-sensitivity landscape.

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