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Novel gene fusions in secretory carcinoma of the salivary glands: enlarging the ETV6 family.
Human Pathology 2018 August 19
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 seven secretory carcinomas with classic ETV6-NTRK3 gene fusion and three secretory carcinomas harboring ETV6-RET gene fusion. In addition, two 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 were 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 has 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.
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