Department of Pathology and Laboratory Medicine, University of British Columbia.
Department of Pathology, Faculty of Medicine in Plzen, Charles University.
Am J Surg Pathol. 2018 Sep;42(9):1182-1189. doi: 10.1097/PAS.0000000000001114.
We describe a novel gene fusion, EWSR1-CREM, identified in 3 cases of clear cell carcinoma (CCC) using anchored multiplex polymerase chain reaction, a next-generation sequencing-based technique. CCC is a low-grade salivary tumor recently characterized to have EWSR1-ATF1 fusions in the majority of cases. Three cases of malignant tumor presenting in the base of tongue, lung, and nasopharynx were studied. All cases shared a clear cell morphology with hyalinized stroma, presence of mucin and p63 positivity and were initially diagnosed as mucoepidermoid carcinoma but were negative for evidence of any of the expected gene fusions. Anchored multiplex polymerase chain reaction demonstrated a EWSR1-CREM fusion in all 3 cases to confirm a diagnosis of CCC. This finding is biologically justified as CREM and ATF1 both belong to the CREB family of transcription factors. EWSR1-CREM fusions have not been previously reported in CCC and have only rarely been reported in other tumors. We show that the ability to discover novel gene variants with next-generation sequencing-based assays has clinical utility in the pathologic classification of fusion gene-associated tumors.
我们描述了一种新型基因融合 EWSR1-CREM，该融合是使用基于锚定多重聚合酶链反应（一种基于下一代测序的技术）在 3 例透明细胞癌（CCC）中发现的。CCC 是一种低级别唾液腺肿瘤，最近的特征是大多数病例存在 EWSR1-ATF1 融合。研究了 3 例位于舌底、肺和鼻咽部的恶性肿瘤。所有病例均具有透明细胞形态，伴透明样基质、黏蛋白存在和 p63 阳性，最初诊断为黏液表皮样癌，但未发现任何预期基因融合的证据。锚定多重聚合酶链反应在所有 3 例中均显示 EWSR1-CREM 融合，以确认 CCC 的诊断。这一发现具有生物学意义，因为 CREM 和 ATF1 均属于 CREB 转录因子家族。EWSR1-CREM 融合在 CCC 中以前未被报道过，在其他肿瘤中也很少被报道过。我们表明，使用基于下一代测序的检测方法发现新型基因变异的能力在融合基因相关肿瘤的病理分类中具有临床应用价值。
