Salivary Secretory Carcinoma Harboring a Novel ALK Fusion Expanding the Molecular Characterization of Carcinomas Beyond the ETV6 Gene
Salivary Secretory Carcinoma Harboring a Novel ALK Fusion Expanding the Molecular Characterization of Carcinomas Beyond the ETV6 Gene
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DOI：
10.1097/pas.0000000000001471
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发表时间：
2020-07-01
影响因子：
5.6
通讯作者：
Hosoda, Waki
中科院分区：
文献类型：
--
作者：
Sasaki, Eiichi;Masago, Katsuhiro;Hosoda, Waki
摘要唾液腺分泌型癌是一种低度恶性的肿瘤，具有明确的形态学及免疫组织化学特徴。在绝大多数SC中检测到ETV 6-NTRK 3融合。最近，在一小部分SC中已经记录了与ETV 6融合的其他伴侣，这表明存在替代性遗传融合。在这项研究中，我们研究了9个SC的基因融合，使用荧光原位杂交，逆转录-聚合酶链反应，和下一代测序（ArcherDx）。在9个SC中的8个中检测到经典ETV 6外显子5-NTRK 3外显子15融合。其余肿瘤的ETV 6-NTRK 3融合为阴性，但含有一种新的融合，CTNNA 1外显子11-ALK外显子20。免疫组化显示，8例ETV 6-NTRK 3融合肿瘤中pan-TRK阳性，而ALK重排SC中pan-TRK阴性，而ALK仅在ALK重排肿瘤中阳性。在组织学上，ALK重排的肿瘤显示出占主导地位的巨囊性结构。总之，我们发现了一例CTNNAl-ALK融合的SC病例。由于ALK侧（酪氨酸激酶结构域上游）20号外显子后的ALK融合已被报道可激活各种ALK重排肿瘤中的致癌激酶，因此ALK抑制剂可能是ALK重排SC的一种可能的治疗选择。此外，ALK免疫组化可作为ALK重排SC的筛查工具。本研究还将该肿瘤的分子谱扩展到ETV 6基因以外。
Secretory carcinoma (SC) of the salivary glands is a low-grade carcinoma characterized by a well-defined morphology and immunohistochemical features. ETV6-NTRK3 fusions are detected in the great majority of SCs. Recently, other partners fused to ETV6 have been documented in a small portion of SCs, suggesting the presence of alternative genetic fusion. In this study, we examined the genetic fusion of 9 SCs using fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and next-generation sequencing (ArcherDx). Classic ETV6 exon 5-NTRK3 exon 15 fusion was detected in 8 of 9 SCs. The remaining tumor was negative for the ETV6-NTRK3 fusion but harbored a novel fusion, CTNNA1 exon 11-ALK in exon 20. Immunohistochemically, pan-TRK was positive in 8 tumors with ETV6-NTRK3 fusion but negative in an ALK-rearranged SC, while ALK was positive only in the ALK-rearranged tumor. Histologically, the ALK-rearranged tumor showed dominant macrocystic architecture. In conclusion, we found a case of SC with CTNNAl-ALK fusion. Because ALK fusion after exon 20 on the ALK side (upstream of the tyrosine kinase domain) has been reported to activate a carcinogenic kinase in various ALK-rearranged tumors, ALK inhibitors may be a possible therapeutic option for ALK-rearranged SC. In addition, ALK immunohistochemistry can be a screening tool for ALK-rearranged SC. This study also expands the molecular spectrum of this tumor beyond the ETV6 gene.