PPP6R3-USP6 amplification: Novel oncogenic mechanism in malignant nodular fasciitis.
Nodular fasciitis (NF) is a clonal self-limited neoplastic proliferation characterized by rearrangements of the USP6 locus in most examples. To our knowledge well-documented malignant behavior has never been previously observed in NF. In this report we present an unusual case of NF with classical histologic features that showed a protracted clinical course characterized by multiple recurrences and eventual metastatic behavior over a period of 10 years. Molecular analyses revealed the presence and amplification of the novel PPPR6-USP6 gene fusion, which resulted in USP6 mRNA transcriptional upregulation. These findings further support the oncogenic role of the USP6 protease in mesenchymal neoplasia and expand the biologic potential of NF. © 2016 Wiley Periodicals, Inc.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.|Department of Dermatology, Mayo Clinic, Rochester, MN.
Ruifeng
R
Guo
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Xiaoke
X
Wang
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.
Margaret M
MM
Chou
Department of Bioinformatics, Mayo Clinic, Rochester, MN.
Yan
Y
Asmann
Department of Diagnostic Radiology, Mayo Clinic, Rochester, MN.
Doris E
DE
Wenger
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Alyaa
A
Al-Ibraheemi
Department of Pathology, Sinai Hospital of Baltimore, Baltimore, MD.
Diana W
DW
Molavi
Department of Orthopaedic, Onology Medstar Franklin Square Hospital, Baltimore, MD.
Albert
A
Aboulafia
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Long
L
Jin
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Karen
K
Fritchie
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Jennifer L
JL
Oliveira
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Robert B
RB
Jenkins
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Jennifer J
JJ
Westendorf
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Jie
J
Dong
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Andre M
AM
Oliveira
D000328:Adult; D063646:Carcinogenesis / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005208:Fasciitis / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
D015514:Oncogene Proteins, Fusion; C433888:PPP6R3 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D010749:Phosphoprotein Phosphatases; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase