Genetic Profiles of Aggressive Variants of Papillary Thyroid Carcinomas.

Aggressive variants of papillary thyroid carcinoma (PTC) have been described with increasing frequency and are associated with unfavorable clinical outcomes. However, limited data exist on the comprehensive genetic profile of these variants. We performed targeted next-generation sequencing in 36 patients with aggressive variants of PTC and compared it to PTC from The Cancer Genome Atlas (TCGA) project and poorly differentiated thyroid cancers (PDTCs)/anaplastic thyroid cancers (ATCs) from the Memorial Sloan Kettering Cancer Center (MSKCC). mutation was the most prevalent (89%) in aggressive variants of PTC compared to that in other thyroid cancers. mutation was identified in one patient (3%), which was less frequent than in others. promoter mutation (17%) ranged between that of PTCs (9%) and PDTCs (40%). Tumor suppressor genes, , and , were mutated in 14%, 3%, and 6% of aggressive variants of PTC, respectively. The mutation rate of (3%) was significantly higher than that of PTCs (0.7%) and lower than that of ATCs (73%). Mutations in three functional groups, histone methyl transferases, SWI/SNF chromatin remodeling complex, and the PI3K/AKT/mTOR pathway, were present in 11%, 14%, and 11% of samples, respectively. In conclusion, aggressive variants of PTC had higher and lower mutation prevalence than other thyroid cancers. The prevalence of mutations in the promoter, , and genes encoding three functional groups ranged between that of PTCs and PDTCs/ATCs.