Abstract 2752: Analysis of epigenetic regulation by mutant p53 gain-of-function in anaplastic thyroid cancer

Thyroid cancer is one of the most common endocrine malignancies. It is primarily classified into four types : papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer and anaplastic thyroid cancer (ATC). Among them, ATC is particularly rare, has a very poor prognosis and is insensitive to conventional treatments. Consequently, the development of effective therapeutic strategies for ATC is urgently needed. Mutations in TP53 have been reported to play a role in the anaplastic transformation of thyroid cancer. TP53 is the most frequently mutated gene across all human cancers. Although common TP53 missense mutations cause loss of its tumor-suppressive function, ‘gain-of-function’ (GOF) mutations of TP53 have recently been reported to promote several types of cancer. Mutant p53 (mut-p53) GOF can manipulate epigenetic regulators and alter the chromatin landscape. However, the impact of mut-p53 GOF on epigenetic regulation in ATC remains unclear. In this study, we aim to elucidate the mechanisms of epigenetic regulation underlying tumor progression driven by mut-p53 GOF in ATC. Hotspot gene mutation analysis revealed the presence of known mut-p53 GOF mutations in three out of seven ATC cell lines. Distribution analysis of ATAC-seq peaks in enhancer regions revealed that certain promising transcription factor binding motifs were enriched in ATC cell lines with mut-p53 GOF. Moreover, we demonstrated that these candidate transcription factors are involved in cell proliferation and migration of ATC cell lines with mut-p53 GOF. These results suggest that the exploration of gene expression regulatory mechanisms by mut-p53 GOF may provide a clue for a novel therapeutic strategy for ATC. Citation Format: Wataru Kawase, Yukihiko Hiroshima, Takashi Oshima, Katsuhiko Masudo, Yohei Miyagi. Analysis of epigenetic regulation by mutant p53 gain-of-function in anaplastic thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2752.