The mutation profile of differentiated thyroid cancer coexisting with undifferentiated anaplastic cancer resembles that
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HUMAN GENETICS • SHORT COMMUNICATION
The mutation profile of differentiated thyroid cancer coexisting with undifferentiated anaplastic cancer resembles that of anaplastic thyroid cancer but not that of archetypal differentiated thyroid cancer Justyna Mika 1 & Wojciech Łabaj 1 & Mykola Chekan 2 Andrzej Polański 1 & Piotr Widłak 2
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Agata Abramowicz 2
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Monika Pietrowska 2
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# The Author(s) 2020
Abstract Differentiated thyroid cancer (DTC) has one of the lowest cancer mutational burdens, while anaplastic thyroid cancer (ATC) has a much higher mutation frequency. A fraction of ATC has an associated differentiated component, which suggests the coevolution of both cancers. Here, we aimed to compare mutation frequency in coexisting ATC and DTC diagnosed concurrently in the same thyroid gland (3 cases) as well as in archetypal DTC and ATC alone (5 cases each). Single-nucleotide variations (SNV) and copy number variations (CNV) were analyzed in each case based on the next-generation sequencing data. We found a similar extent of mutational events, both SNV and CNV, in undifferentiated and differentiated components of thyroid cancers coexisting in one patient. The magnitude of these mutations was comparable to the level of mutations observed in ATC alone; yet, it was much higher than in archetypal DTC. This suggested that, despite histopathological features of differentiated tumors, molecular characteristics of such cancers coexisting with ATC and archetypal DTC could be significantly different. Pairwise comparison of mutational profiles of coexisting cancers enabled assumption on the possible evolution of both components, which appeared distinct in 3 analyzed cases. This included independent development of ATC and DTC diagnosed concurrently in two lobes of the same thyroid, as well as the development of anaplastic and differentiated cancer from the common ancestor that putatively gained a key driver mutation (BRAFV600E or KRASQ61R), which was followed either by early or late molecular separation of both cancers. Keywords Cancer evolution . Concurrent cancers . Mutation profiles . Next-generation sequencing . Thyroid cancer
Introduction Thyroid cancer represents a wide spectrum of malignancies, among which the most frequent are papillary thyroid carcinomas (PTC) and follicular thyroid carcinomas (FTC), Justyna Mika, Wojciech Łabaj and Mykola Chekan contributed equally to this work. * Andrzej Polański [email protected] * Piotr Widłak [email protected] 1
Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, Gliwice, Poland
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Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
collectively termed “differentiated thyroid carcinomas” (DTC), which generally have low mortality and high curability (Siegel et al. 2015). On the other hand, undifferentiated anaplastic thyroid carcinoma (ATC), though very rare, is very aggressive and nearly universally fatal (Chiacchio et al. 2008). Epidemiological, clinical, and pathol
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