Establishment and Characterization of OK-ATC1 and OK-ATC1-PDX: a Novel Cell Line and Patient-Derived Xenograft Model of BRAF V600E-Mutated Anaplastic Thyroid Carcinoma

Abstract Anaplastic thyroid carcinoma (ATC) is characterized by rapid progression, marked biological heterogeneity, and rarity, which makes clinical studies difficult to conduct. The development of novel therapeutic strategies for ATC thus requires appropriate experimental animal models. We established a novel ATC cell line (OK-ATC1) and corresponding patient-derived xenograft (PDX) model (OK-ATC1-PDX) from an 89-year-old Japanese female patient. The patient’s ATC was diagnosed as having arisen from transformation of papillary thyroid carcinoma. Both the newly established cell line and PDX model successfully retained the immunohistochemical and genetic profiles of the clinical ATC component. Immunophenotypically, the models were p53-negative, PAX8-positive, and TTF-1–negative. Genetic profiling revealed that both OK-ATC1 and OK-ATC1-PDX maintained key driver mutations identified in the primary tumor, including BRAF V600E, TERT promoter − 146C > T, and TP53 V73fs*50. To our knowledge, this is the first reported ATC-PDX model harboring a TERT promoter − 146C > T mutation, and this is one of the few studies to have simultaneously established both an ATC cell line and PDX model. These newly developed and well-characterized models are expected to serve as valuable platforms for accelerating the development of novel therapeutic strategies for ATC.