Molecular Profiling of Hyalinizing Clear Cell Carcinomas Revealed a Subset of Tumors Harboring a Novel EWSR1-CREM Fusion Report of 3 Cases
Molecular Profiling of Hyalinizing Clear Cell Carcinomas Revealed a Subset of Tumors Harboring a Novel EWSR1-CREM Fusion Report of 3 Cases
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DOI：
10.1097/pas.0000000000001114
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发表时间：
2018-09-01
影响因子：
5.6
通讯作者：
Ng, Tony L.
中科院分区：
文献类型：
--
作者：
Chapman, Erin;Skalova, Alena;Ng, Tony L.
我们描述了一种新型基因融合体 EWSR1-CREM，它是使用锚定多重聚合酶链式反应（一种新一代基于测序的技术）在 3 例透明细胞癌 (CCC) 病例中发现的。 CCC 是一种低度唾液腺肿瘤，最近在大多数病例中发现具有 EWSR1-ATF1 融合。研究了三例舌根、肺、鼻咽部恶性肿瘤。所有病例均具有透明基质的透明细胞形态，存在粘蛋白和 p63 阳性，最初被诊断为粘液表皮样癌，但任何预期基因融合的证据均为阴性。锚定多重聚合酶链反应证实所有 3 例患者均存在 EWSR1-CREM 融合，从而证实了 CCC 的诊断。这一发现在生物学上是合理的，因为 CREM 和 ATF1 都属于转录因子 CREB 家族。 EWSR1-CREM 融合以前未在 CCC 中报道过，并且在其他肿瘤中也很少报道。我们证明，通过下一代测序检测发现新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实用性。
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.