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 (BRAF^V600E or KRAS^Q61R), which was followed either by early or late molecular separation of both cancers.

分化型甲状腺癌 (DTC) 具有最低的癌症突变负荷之一，而间变性甲状腺癌 (ATC) 具有更高的突变频率。一部分 ATC 具有相关的分化成分，这表明两种癌症的共同进化。在这里，我们的目的是比较在同一甲状腺（3 例）中同时诊断出的共存 ATC 和 DTC 以及单独的原型 DTC 和 ATC（各 5 例）中的突变频率。单核苷酸变异 (SNV) 和拷贝数变异 (CNV) 在每种情况下都基于下一代测序数据进行分析。我们在一名患者共存的甲状腺癌的未分化和分化成分中发现了相似程度的突变事件，包括 SNV 和 CNV。这些突变的幅度与单独在 ATC 中观察到的突变水平相当；然而，它比原型 DTC 高得多。这表明，尽管分化肿瘤具有组织病理学特征，但与 ATC 和原型 DTC 共存的此类癌症的分子特征可能存在显着差异。对共存癌症的突变谱进行成对比较，可以假设两种成分的可能演变，这在 3 个分析案例中似乎不同。这包括在同一甲状腺的两个叶中同时诊断出的 ATC 和 DTC 的独立发展，以及来自假定获得关键驱动突变的共同祖先的间变性和分化癌症的发展。这种与 ATC 和原型 DTC 共存的癌症的分子特征可能有显着差异。对共存癌症的突变谱进行成对比较，可以假设两种成分的可能进化，这在 3 个分析案例中似乎不同。这包括在同一甲状腺的两个叶中同时诊断出的 ATC 和 DTC 的独立发展，以及来自假定获得关键驱动突变的共同祖先的间变性和分化癌症的发展。这种与 ATC 和原型 DTC 共存的癌症的分子特征可能有显着差异。对共存癌症的突变谱进行成对比较，可以假设两种成分的可能演变，这在 3 个分析案例中似乎不同。这包括在同一甲状腺的两个叶中同时诊断出的 ATC 和 DTC 的独立发展，以及来自假定获得关键驱动突变的共同祖先的间变性和分化癌症的发展。BRAF ^V600E或KRAS ^Q61R），随后是两种癌症的早期或晚期分子分离。