TITLE: “Characterization of Genomics Landscape and Natural History of Anaplastic Thyroid Cancer using High Depth WGS and Subclonal Reconstruction.”
ABSTRACT: Anaplastic thyroid cancer (ATC) is among the most lethal cancer types, with a median survival rate of approximately 12 weeks. ATC is resistant to both chemo- and radiotherapy, a characteristic attributed to its surrounding tissues and rapid progression. Although ATC is less common than other thyroid cancers, such as papillary thyroid carcinoma (PTC) and differentiated thyroid carcinoma (DTC), it frequently co-occurs with both PTC and DTC. In this study, we assembled a 108-sample cohort consisting of 46 ATC patients and 5 thyroid cancer cell lines. We conducted high-depth (x90) whole genome sequencing on ATC samples, as well as on adjacent PTC or DTC tissues, and included blood controls when available. Our analysis identified both germline and somatic variants in ATC, revealing a moderate mutation burden compared to C-type tumors and a higher incidence of recurrent SNVs and CNVs than in PTC or DTC. Notably, ATC samples exhibited more active mutational signatures, such as SBS2 and SBS13, than DTC or PTC samples. Additionally, we employed subclonal reconstruction to model the natural history of ATC in relation to cooccurring DTC and PTC.
