Department of Otolaryngology - Head and Neck Surgery, Western University, London, ON, Canada; London Regional Cancer Program, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada.
Ontario Institute for Cancer Research, Toronto, ON, Canada; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Cell Rep. 2024 Mar 26;43(3):113826. doi: 10.1016/j.celrep.2024.113826. Epub 2024 Feb 26.
Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.
间变性甲状腺癌可以说是最致命的人类恶性肿瘤。它常与分化型甲状腺癌同时发生，但目前尚不清楚其侵袭性的分子起源。我们对包括 213 例原发性间变性甲状腺癌患者在内的 329 个甲状腺癌区域的肿瘤 DNA 进行了测序。我们还对 9 名患者使用分化型和间变性甲状腺癌成分的多区域测序进行了全基因组测序。利用这些数据，我们证明间变性甲状腺癌的突变负担高于其他甲状腺癌，具有不同的突变特征和分子亚型。此外，不同的癌症驱动基因在间变性和分化型甲状腺癌中发生突变，即使它们发生在单个患者中。最后，我们明确证明间变性甲状腺癌与同时发生的分化型癌具有共同的基因组起源，并通过获得特征性克隆驱动突变从共同的恶性区域中出现。
