Institute of Pathology, University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia.
Department of Orthopedic Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Genes Chromosomes Cancer. 2020 Jun;59(6):357-365. doi: 10.1002/gcc.22836. Epub 2020 Feb 8.
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.
动脉瘤样骨囊肿（ABC）是一种良性但局部侵袭性肿瘤，具有局部复发的倾向。与其他具有继发性囊变的骨肿瘤不同，ABC 的特征在于 USP6 基因重排。目前已知有越来越多的 USP6 融合伙伴，随着下一代测序（NGS）的出现，对其特征的描述成为可能。已知的融合伙伴包括 CDH11、CNBP、COL1A1、CTNNB1、EIF1、FOSL2、OMD、PAFAH1B1、RUNX2、SEC31A、SPARC、STAT3、THRAP3 和 USP9X。我们使用 NGS 分析了连续的 11 例 ABC，并在所有病例中均发现 USP6 融合，这进一步证明 USP6 融合普遍存在于原发性 ABC 中。我们在 5 例 ABC 中发现了 4 个新的融合伙伴，并通过 RT-PCR 和 Sanger 测序进行了确认，分别是 ASAP1、FAT1、SAR1A 和 TNC（两种情况）。由于 NGS 检测 USP6 融合具有高灵敏度和特异性，因此可能有助于区分 ABC 和其类似物，尤其是在仅通过形态学无法明确诊断的小活检样本中。需要进行更多病例和随访的研究，以确定不同的融合伙伴是否与 ABC 的特定临床和病理特征相关。
