TG-IGF1R: A Novel Receptor Tyrosine Kinase Fusion Oncogene in Pediatric Thyroid Cancer.

BACKGROUND

Receptor Tyrosine Kinase (RTK) fusions of RET, NTRK1/3, and ALK are enriched among pediatric thyroid cancer patients with metastatic and persistent disease and their oncoproteins represent attractive drug targets.

METHODS

We performed RNA-sequencing in a papillary thyroid cancer lacking other frequent driver alterations.

RESULTS

We report a novel RTK fusion, TG-IGF1R, in a 17-year-old female patient with angioinvasive follicular variant papillary thyroid cancer. The in-frame fusion protein preserves the cholinesterase-like domain of TG with dimerization properties and the transmembrane and kinase domain of IGF1R. The tumor sample shows increased IGF1R mRNA expression and tyrosine kinase phosphorylation, augmentation of MAPK transcriptional output genes and decreased NIS levels.

CONCLUSIONS

We reveal a novel targetable kinase fusion oncogene in thyroid cancer which is not incorporated in different thyroid-specific sequencing panels. The integration of IGF1R fusion screening in the next versions of thyroid-specific targeted NGS panels may be beneficial to thyroid cancer patients.