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Significance Thyroid cancer is common and has an excellent outcome in many cases, although a proportion of these tumors have a progressive clinical course and high mortality. Using whole-transcriptome (RNA-sequencing) analysis, we discovered previously unknown genetic events, anaplastic lymphoma kinase (ALK ) gene fusions, in thyroid cancer and demonstrate that they occur more often in aggressive cancers. The most common fusion identified in these tumors involved the striatin (STRN ) gene, and we show that it is transforming and tumorigenic in vivo. Finally, we demonstrate that the kinase activity of STRN-ALK can be blocked by ALK inhibitors, raising a possibility that ALK fusions may be used as a therapeutic target for patients with the most aggressive and frequently lethal forms of thyroid cancer.

Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer