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Fusion Oncogenes in Salivary Gland Tumors: Molecular and Clinical Consequences

  • Invited Review: An Update on Salivary Gland Pathology
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Abstract

Salivary gland tumors constitute a heterogeneous group of uncommon diseases that pose significant diagnostic and therapeutic challenges. However, the recent discovery of a translocation-generated gene fusion network in salivary gland carcinomas as well in benign salivary gland tumors opens up new avenues for improved diagnosis, prognostication, and development of specific targeted therapies. The gene fusions encode novel fusion oncoproteins or ectopically expressed normal or truncated oncoproteins. The major targets of the translocations are transcriptional coactivators, tyrosine kinase receptors, and transcription factors involved in growth factor signaling and cell cycle regulation. Notably, several of these targets or pathways activated by these targets are druggable. Examples of clinically significant gene fusions in salivary gland cancers are the MYB–NFIB fusion specific for adenoid cystic carcinoma, the CRTC1–MAML2 fusion typical of low/intermediate-grade mucoepidermoid carcinoma, and the recently identified ETV6–NTRK3 fusion in mammary analogue secretory carcinoma. Similarly, gene fusions involving the PLAG1 and HMGA2 oncogenes are specific for benign pleomorphic adenomas. Continued studies of the molecular consequences of these fusion oncoproteins and their down-stream targets will ultimately lead to the identification of novel driver genes in salivary gland neoplasms and will also form the basis for the development of new therapeutic strategies for salivary gland cancers and, perhaps, other neoplasms.

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Acknowledgments

I thank Marta Persson for excellent help with the illustrations. Work presented in this review was supported by the Swedish Cancer Society, IngaBritt and Arne Lundberg Research Foundation, the Adenoid Cystic Carcinoma Research Foundation, and BioCARE—a National Strategic Cancer Research program at University of Gothenburg.

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  1. Department of Pathology, Sahlgrenska Cancer Center, University of Gothenburg, Box 425, 405 30, Göteborg, Sweden

    Göran Stenman

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Stenman, G. Fusion Oncogenes in Salivary Gland Tumors: Molecular and Clinical Consequences. Head and Neck Pathol 7 (Suppl 1), 12–19 (2013). https://doi.org/10.1007/s12105-013-0462-z

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