Department of Pathology, Massachusetts General Hospital, Boston, MA 02114-2696, USA; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Department of Pathology, Massachusetts General Hospital, Boston, MA 02114-2696, USA; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Hum Pathol. 2019 Jan;83:50-58. doi: 10.1016/j.humpath.2018.08.011. Epub 2018 Aug 18.
Secretory carcinoma (SC) of the salivary gland is a low-grade malignancy associated with a well-defined clinical, histologic, immunohistochemical, and cytogenetic signature. Although the t(12;15) (p13;q25) translocation resulting in an ETV6-NTRK3 gene fusion is well documented, advances in molecular profiling in salivary gland tumors have led to the discovery of RET as another ETV6 gene fusion partner in SC. Here, we applied an RNA-based next-generation sequencing (NGS) approach for fusion detection on 14 presumed SC. The cases included 7 SC with classic ETV6-NTRK3 gene fusion and 3 SC harboring ETV6-RET gene fusion. In addition, 2 cases revealed a NCOA4-RET gene fusion and were subsequently reclassified as intraductal carcinomas. One case with an unusual dual-pattern morphology revealed a novel translocation involving ETV6, NTRK3, and MAML3 gene rearrangements. Interestingly, no ETV6-NTRK3 or ETV6-RET SC was ever documented to have this unique dual-pattern morphology or harbor a MAML3 mutation. The remaining case had no detected chromosomal abnormalities. Advances in molecular profiling of SC have led to the discovery of novel fusion partners such as RET and now MAML3. Further molecular characterization of salivary gland neoplasms is needed as these mutations may present alternative therapeutic targets in patients with these tumors.
涎腺分泌癌（SC）是一种低度恶性肿瘤，具有明确的临床、组织学、免疫组织化学和细胞遗传学特征。尽管 t(12;15)(p13;q25)易位导致 ETV6-NTRK3 基因融合已得到充分证实，但在涎腺肿瘤的分子谱分析方面的进展导致了 RET 作为另一个 ETV6 基因融合伙伴在 SC 中的发现。在这里，我们应用基于 RNA 的下一代测序（NGS）方法对 14 例疑似 SC 进行融合检测。这些病例包括 7 例具有经典 ETV6-NTRK3 基因融合的 SC 和 3 例具有 ETV6-RET 基因融合的 SC。此外，2 例显示 NCOA4-RET 基因融合，随后被重新分类为导管内癌。1 例具有不寻常的双重形态学表现的病例揭示了一种涉及 ETV6、NTRK3 和 MAML3 基因重排的新型易位。有趣的是，从未有过记录表明具有这种独特双重形态学表现或携带 MAML3 突变的 ETV6-NTRK3 或 ETV6-RET SC。其余病例未检测到染色体异常。SC 的分子谱分析的进展导致了新的融合伙伴的发现，如 RET 和现在的 MAML3。需要进一步对涎腺肿瘤进行分子特征分析，因为这些突变可能为这些肿瘤患者提供替代的治疗靶点。
