Primary aneurysmal bone cyst with a novel SPARC-USP6 translocation identified by next-generation sequencing

Šekoranja, Daja; Boštjančič, Emanuela; Salapura, Vladka; Mavčič, Blaž; Pižem, Jože

doi:10.1016/j.cancergen.2018.07.001

Cited by 27 publications

(34 citation statements)

References 12 publications

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“…In 8 of 10 cases, excluding the previously published case, microscopic findings were typical of an ABC and included an exclusively or predominantly cystic morphology with nodular fasciitis‐like areas, osteoclast‐like giant cells, hemosiderin deposition, deposition of woven bone beneath the surface of septal structures and focal matrix calcification in 4 cases. There were focal solid areas in two cases, representing approximately 25% of the lesions (Table ).…”

Section: Resultsmentioning

confidence: 92%

“…Identification of novel USP6 ‐fusion partners in four of five prospectively analyzed primary ABCs (including a previously reported case) prompted us to analyze systematically a series of consecutive primary ABCs for the presence of USP6 fusions and USP6 fusion partners. We identified 11 recent cases of ABCs with histopathologic and radiologic features consistent with primary ABCs (including five prospectively analyzed cases), diagnosed at the Institute of Pathology, University of Ljubljana, Faculty of Medicine, between January 2016 and September 2019.…”

Section: Methodsmentioning

confidence: 99%

“…The quantity and quality of isolated RNA was determined using a Nano‐Drop‐1000 spectrophotometer and Qubit 3.0 fluorimeter (both from Thermo Fisher Scientific, Waltham, MA). NGS analysis was performed using an ArcherDX FusionPlex Sarcoma Kit (ArcherDX, Boulder, CO) on the Ion Torrent S5 NGS system (Thermo Fischer Scientific, Waltham, MA) as described previously …”

Section: Methodsmentioning

confidence: 99%

“…Other bone lesions may morphologically mimic ABC, in particular when they undergo ABC‐like cystic change (also referred to as secondary ABCs), including giant cell tumor, osteoblastoma, chondroblastoma, fibrous dysplasia, and osteosarcoma . Solid variant ABC may be particularly difficult to differentiate, both radiologically and histologically, from other bone lesions …”

Section: Introductionmentioning

confidence: 99%

“…There is a growing list of known fusion partners, of which CDH11 seems to be the most frequent; it was detected in 19% and 38% of ABCs in two series . Other fusion partners identified so far include CNBP , COL1A1 , OMD and THRAP3 , CTNNB1 , E1F1 , FOSL2 , PAFAH1B1 , RUNX2 , SEC31A , STAT3 , SPARC and, most recently, USP9X . Despite different fusion partners, all USP6 rearrangements seem to function by a promoter swap mechanism, resulting in oncogenic activation of USP6 and subsequent ABC formation .…”

Section: Introductionmentioning

confidence: 99%

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Novel ASAP1‐USP6, FAT1‐USP6, SAR1A‐USP6, and TNC‐USP6 fusions in primary aneurysmal bone cyst

Šekoranja

Zupan

Mavčič

et al. 2020

Genes Chromosomes & Cancer

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Aneurysmal bone cyst (ABC) is a benign but locally aggressive neoplasm, with a tendency for local recurrence. In contrast to other bone tumors with secondary cystic change, ABC is characterized by USP6 gene rearrangement. There is a growing list of known USP6 fusion partners, characterization of which has been enabled with the advent of next‐generation sequencing (NGS). The list of known fusion partners includes CDH11, CNBP, COL1A1, CTNNB1, EIF1, FOSL2, OMD, PAFAH1B1, RUNX2, SEC31A, SPARC, STAT3, THRAP3, and USP9X. Using NGS, we analyzed a series of 11 consecutive ABCs and identified USP6 fusions in all cases, providing further evidence that USP6 fusions are universally present in primary ABCs. We identified four novel fusion partners in five ABCs and confirmed them by RT‐PCR and Sanger sequencing, ASAP1, FAT1, SAR1A, and TNC (in two cases). Because of high sensitivity and specificity, detection of a USP6 fusion by NGS may assist in differentiating between ABC and its mimics, especially in small biopsy samples when a definite diagnosis cannot be achieved on morphological grounds alone. Further studies with a large number of cases and follow‐up are needed to determine whether different fusion partners are associated with specific clinical and pathologic features of ABCs.

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Section: Resultsmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel ASAP1‐USP6, FAT1‐USP6, SAR1A‐USP6, and TNC‐USP6 fusions in primary aneurysmal bone cyst

Šekoranja

Zupan

Mavčič

et al. 2020

Genes Chromosomes & Cancer

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RNA sequencing identifies a novel USP9X‐USP6 promoter swap gene fusion in a primary aneurysmal bone cyst

Blackburn

Davila

Jackson

et al. 2019

Genes Chromosomes & Cancer

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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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Benigne Knochentumoren im Kindesalter

Bergovec,

Smolle,

Leithner

2023

Orthopädie Und Unfallchirurgie

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Primary aneurysmal bone cyst with a novel SPARC-USP6 translocation identified by next-generation sequencing

Cited by 27 publications

References 12 publications

Novel ASAP1‐USP6, FAT1‐USP6, SAR1A‐USP6, and TNC‐USP6 fusions in primary aneurysmal bone cyst

Novel ASAP1‐USP6, FAT1‐USP6, SAR1A‐USP6, and TNC‐USP6 fusions in primary aneurysmal bone cyst

RNA sequencing identifies a novel USP9X‐USP6 promoter swap gene fusion in a primary aneurysmal bone cyst

Benigne Knochentumoren im Kindesalter

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