Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion

Lab Invest. 2011 Oct;91(10):1427-33. doi: 10.1038/labinvest.2011.118. Epub 2011 Aug 8.


Nodular fasciitis (NF) is a relatively common mass-forming and self-limited subcutaneous pseudosarcomatous myofibroblastic proliferation of unknown pathogenesis. Due to its rapid growth and high mitotic activity, NF is often misdiagnosed as a sarcoma. While studying the USP6 biology in aneurysmal bone cyst and other mesenchymal tumors, we identified high expression levels of USP6 mRNA in two examples of NF. This finding led us to further examine the mechanisms underlying USP6 overexpression in these lesions. Upon subsequent investigation, genomic rearrangements of the USP6 locus were found in 92% (44 of 48) of NF. Rapid amplification of 5'-cDNA ends identified MYH9 as the translocation partner. RT-PCR and direct sequencing revealed the fusion of the MYH9 promoter region to the entire coding region of USP6. Control tumors and tissues were negative for this fusion. Xenografts of cells overexpressing USP6 in nude mice exhibited clinical and histological features similar to human NF. The identification of a sensitive and specific abnormality in NF holds the potential to be used diagnostically. Considering the self-limited nature of the lesion, NF may represent a model of 'transient neoplasia', as it is, to our knowledge, the first example of a self-limited human disease characterized by a recurrent somatic gene fusion event.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Base Sequence
  • Cadherins / metabolism
  • Child
  • Child, Preschool
  • Collagen Type I / metabolism
  • Fasciitis / genetics*
  • Fasciitis / pathology*
  • Female
  • Gene Expression Profiling
  • Gene Fusion*
  • Gene Rearrangement
  • Genome, Human / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Molecular Motor Proteins / genetics*
  • Molecular Motor Proteins / metabolism
  • Myosin Heavy Chains / genetics*
  • Myosin Heavy Chains / metabolism
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma / diagnosis
  • Translocation, Genetic
  • Transplantation, Heterologous
  • Ubiquitin Thiolesterase / genetics*
  • Ubiquitin Thiolesterase / metabolism
  • Up-Regulation
  • Young Adult


  • Cadherins
  • Collagen Type I
  • MYH9 protein, human
  • Molecular Motor Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • collagen type I, alpha 1 chain
  • osteoblast cadherin
  • USP6 protein, human
  • Ubiquitin Thiolesterase
  • Myosin Heavy Chains