The genomic and evolutionary landscapes of anaplastic thyroid carcinoma

作者：Peter YF. Zeng, Stephenie D. Prokopec, Stephen Y. Lai, Nicole Pinto, Michelle Chan‐Seng‐Yue, Roderick Clifton‐Bligh, Michelle D. Williams, Christopher J. Howlett, Paul Plantinga, Matthew J. Cecchini, Alfred K. Lam, Iram Siddiqui, Jianxin Wang, Ren Sun, John D. Watson, Reju Korah, Tobias Carling, Nishant Agrawal, Nicole A. Cipriani, Douglas W. Ball, Barry D. Nelkin, Lisa M. Rooper, Justin A. Bishop, Cathie Garnis, Ken Berean, Norman G. Nicolson, Paul Weinberger, Ying C. Henderson, Christopher M. Lalansingh, Mao Tian, Takafumi N. Yamaguchi, Julie Livingstone, Adriana Salcedo, Krupal Patel, Frederick S. Vizeacoumar, Alessandro Datti, Xi Liu, Yuri E. Nikiforov, Robert C. Smallridge, John A. Copland, Laura A. Marlow, Martin Hyrcza, Leigh Delbridge, Stan B. Sidhu, Mark Sywak, Bruce Robinson, Kevin Fung, Farhad Ghasemi, Keith Kwan, S. Danielle MacNeil, Adrian Mendez, David A. Palma, Mohammed Imran Khan, Mushfiq Hassan Shaikh, Kara M. Ruicci, Bret Wehrli, Eric Winquist, John Yoo, Joe S. Mymryk, James W. Rocco, David A. Wheeler, Steve Scherer, Thomas J. Giordano, John W. Barrett, William C. Faquin, Anthony J. Gill, Gary L. Clayman, Paul C. Boutros, Anthony C. Nichols · 发表于：Cell Reports · 年份：2024 · DOI：10.1016/j.celrep.2024.113826 · 被引用次数：78 · 研究领域：Thyroid Cancer Diagnosis and Treatment、BRCA gene mutations in cancer、Genetic factors in colorectal cancer

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.