ETV6-NTRK3 and STRN-ALK kinase fusions are recurrent events in papillary thyroid cancer of adult population

<jats:sec> <jats:title>Objective</jats:title> <jats:p>PTC-specific analysis identified novel fusions involving <jats:italic>RET</jats:italic>, <jats:italic>BRAF</jats:italic>, <jats:italic>NTRK1</jats:italic>, <jats:italic>NTRK3</jats:italic>, <jats:italic>AGK</jats:italic> and <jats:italic>ALK</jats:italic> genes in adults and pediatric PTCs. Although many novel fusions are PTC-specific events and, therefore, are ideal for diagnosis purposes, validation across additional and larger patient cohorts is essential for introducing these potential diagnostic or prognostic biomarkers into the clinical practice. As most of the <jats:italic>BRAF</jats:italic>, <jats:italic>NTRK3</jats:italic> and <jats:italic>ALK</jats:italic> fusions were initially found in pediatric PTC or in more aggressive thyroid carcinomas, and there is a great disparity across population, in this study, we screened a large set of adult-sporadic PTC cases for the most prevalent kinase fusion lately described in the TCGA.</jats:p></jats:sec> <jats:sec> <jats:title>Design and methods</jats:title> <jats:p>The prevalence of the fusions was determined by RT-PCR in 71 classical PTC, 45 follicular variants of PTC (FVPTC), 19 follicular thyroid adenomas (FTAs) and 22 follicular thyroid carcinomas (FTCs).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p><jats:italic>ETV6–NTRK3</jats:italic> was exclusively found in FVPTC, in both encapsulated and infiltrative variants, but was not found in FTAs and FTCs. <jats:italic>STRN-ALK</jats:italic> was found in both classical PTC and FVPTC. No <jats:italic>AGK-BRAF</jats:italic> fusion was identified in this series, endorsing that <jats:italic>AGK–BRAF</jats:italic> is a genetic event mainly associated with pediatric PTCs.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The identification of kinase fusions in thyroid carcinomas helps to expand our knowledge about the landscape of oncogenic alterations in PTC. As <jats:italic>ETV6–NTRK3</jats:italic> and <jats:italic>STRN–ALK</jats:italic> are recurrent and not identified in benign lesions, they can certainly help with diagnosis of thyroid nodules. Further analysis is needed to define if they can also be useful for prognosis and guiding therapy.</jats:p> </jats:sec>