Article

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

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Laboratory Investigation (Impact Factor: 3.68). 08/2011; 91(10):1427-33. DOI: 10.1038/labinvest.2011.118
Source: PubMed

ABSTRACT

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.

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    • "This lesion was often misdiagnosed as a sarcoma because of its rapid growth, rich cellularity, and mitotic activity [1,2]. Recently USP6 rearrangement and MYH9-USP6 gene fusions have been identified in a high percentage of NF suggestive that this is the driving translocation [3]. Histologically, NF is mainly made up of plump myofibroblasts which resemble the fibroblasts in tissue culture or granulation tissue, and the background is variably myxoid or fibrous [4]. "
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