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

• Published in: Genes chromosomes & cancer Vol. 59; no. 6; pp. 357 - 365
• Main Authors: Šekoranja, Daja, Zupan, Andrej, Mavčič, Blaž, Martinčič, David, Salapura, Vladka, Snoj, Žiga, Limpel Novak, Ana K., Pižem, Jože
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-06-2020; Wiley Subscription Services, Inc
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adolescent; Adult; Aged; Aneurysm; aneurysmal bone cyst; ASAP1‐USP6; Biopsy; Bone Cysts, Aneurysmal - genetics; Bone Cysts, Aneurysmal - pathology; Bone tumors; Cadherins - genetics; Cbfa-1 protein; Child; Child, Preschool; Collagen (type I); Cysts; FAT1‐USP6; Female; Gene Fusion; Gene rearrangement; Humans; Male; Middle Aged; Monomeric GTP-Binding Proteins - genetics; next‐generation sequencing; Osteonectin; SAR1A‐USP6; Stat3 protein; Tenascin - genetics; TNC‐USP6; Ubiquitin Thiolesterase - genetics; aneurysmal bone cyst; SAR1A-USP6; FAT1-USP6; ASAP1-USP6; next-generation sequencing; TNC-USP6
• ISSN: 1045-2257; 1098-2264
• DOI: 10.1002/gcc.22836

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.