Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies and Mutations as Negative Survival Predictors.

Anaplastic thyroid carcinoma (ATC) is rare but highly aggressive. We investigated the association of selected driver mutations, including , , promoter, , , and mismatch repair deficiency (MMR-D) with the clinicopathological features of ATC to identify prognostic and predictive biomarkers. Thirty-nine retrospective cases from pathology archives were enrolled for clinicopathology analysis and immunohistochemistry, and 27 cases had sufficient specimens for further molecular testing using targeted next-generation sequencing and mass spectrometry. and mutations were identified in 25.9% and 40.7% of ATC, respectively. mutation was significantly associated with coexisting papillary thyroid carcinoma ( = 0.009) and mutations with female gender ( = 0.012). In univariant analysis, the non- tumors were significantly associated with the presence of a sarcomatoid pattern ( = 0.045). , promoter, and mutations were identified in 14.8%, 81.5%, and 70.4% of cases, respectively. No MMR-D or mutations were detected. In survival analyses, and mutations were significantly associated with inferior outcomes ( = 0.03 and = 0.006, respectively). In conclusion, driver mutations in ATC are associated with distinct clinicopathological features. and mutations were negative predictors for patient survival. Emerging therapeutic agents targeting BRAF, RAS, and PI3 kinase may benefit a substantial proportion of ATC patients.