Anaplastic thyroid cancer (ATC) is a lethal human cancer with a 5-year survival rate of less than 10%. Recently, its genomic and transcriptomic characteristics have been extensively elucidated over 5 years owing to advance in high throughput sequencing. These efforts have extended molecular understandings into the progression mechanisms and therapeutic vulnerabilities of aggressive thyroid cancers. In this review, we provide an overview of genomic and transcriptomic alterations in ATC and poorly-differentiated thyroid cancer, which are distinguished from differentiated thyroid cancers. Clinically relevant genomic alterations and deregulated signaling pathways will be able to shed light on more effective prevention and stratified therapeutic interventions for affected patients.

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Since the release of The Cancer Genome Atlas study of papillary thyroid carcinoma (PTC) in 2014, additional genomic studies of differentiated thyroid carcinoma (DTC) using massively-parallel sequencing (MPS) have been published. Recent advances in MPS technology have started to provide important insights into the molecular pathogenesis of DTC. In the genomic landscape, the most recurrently altered genes in DTC, which has a low mutational burden relative to other cancers, are BRAF, RAS, and fusion genes. Some novel driver candidates also have been identified. The frequency of these genomic alterations varies across the subtypes of DTC (classical PTC, follicular variant of PTC, and follicular thyroid carcinoma). Telomerase reverse transcriptase (TERT) promoter mutations are the alteration that makes the most important contribution to the progression of DTC. In the transcriptomic landscape, DTC can be classified according to its gene expression profile, and each subtype has a distinct mutational profile, intracellular signaling output, and clinicopathological characteristics. Herein, we review the results of genomic studies using MPS technology, and describe the types and frequencies of genomic alterations according to histological classifications of DTC and the characteristics and significance of the gene expression signatures of DTC.

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