RNA sequencing identifies a novel USP9X-USP6 promoter swap gene fusion in a primary aneurysmal bone cyst
Patrick R. Blackburn
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorJaime I. Davila
Department of Health Science Research, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorRory A. Jackson
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorNumrah Fadra
Department of Health Science Research, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorMazen A. Atiq
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorBeth A. Pitel
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorAsha A. Nair
Department of Health Science Research, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorTodd J. VanDeWalker
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorMark G. Hessler
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorSara K. Hovel
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorRebecca N. Wehrs
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorKaren J. Fritchie
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorRobert B. Jenkins
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorKevin C. Halling
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorCorresponding Author
Katherine B. Geiersbach
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Correspondence
Katherine B. Geiersbach, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
Email: [email protected]
Search for more papers by this authorPatrick R. Blackburn
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorJaime I. Davila
Department of Health Science Research, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorRory A. Jackson
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorNumrah Fadra
Department of Health Science Research, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorMazen A. Atiq
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorBeth A. Pitel
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorAsha A. Nair
Department of Health Science Research, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorTodd J. VanDeWalker
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorMark G. Hessler
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorSara K. Hovel
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorRebecca N. Wehrs
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorKaren J. Fritchie
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorRobert B. Jenkins
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorKevin C. Halling
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Search for more papers by this authorCorresponding Author
Katherine B. Geiersbach
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Correspondence
Katherine B. Geiersbach, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
Email: [email protected]
Search for more papers by this authorAbstract
Primary aneurysmal bone cyst (ABC) is a benign multiloculated cystic lesion of bone that is defined cytogenetically by USP6 gene rearrangements. Rearrangements involving USP6 are promoter swaps, usually generated by fusion of the noncoding upstream exons of different partner genes with exon 1 or 2 of USP6, thus leading to transcriptional upregulation of full-length USP6 coding sequence. Testing for USP6 rearrangements is used diagnostically to distinguish it from secondary ABC and other giant cell-rich primary bone tumors. In this report, we present a case of a 16-year-old male with a primary ABC of the left distal femur. USP6 break apart fluorescence in situ hybridization was positive for a rearrangement and conventional chromosome analysis identified a reciprocal X;17 translocation. In order to identify the putative USP6 fusion partner, we performed RNA sequencing and uncovered a novel USP9X-USP6 promoter swap fusion. This result was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and by mate pair sequencing thus showing the utility of these alternative methodologies in identifying novel fusion candidates. Ubiquitin-specific protease 9X (USP9X), like USP6, encodes a highly conserved substrate-specific deubiquitylating enzyme. USP9X is highly expressed in a number of tissue types and acts as both an oncogene and tumor suppressor in several human cancers. We conclude that oncogenic activation of USP6 via USP9X promoter exchange represents a novel driver of primary ABC formation.
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