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Zeng, Peter Y.F.; Prokopec, Stephenie D.; Lai, Stephen Y.; Pinto, Nicole; Chan-Seng-Yue, Michelle A.; Clifton-Bligh, Roderick; Williams, Michelle D.; Howlett, Christopher J.; Plantinga, Paul; Cecchini, Matthew J.; Lam, Alfred K.; Siddiqui, Iram; Wang, Jianxin; Sun, Ren X.; Watson, John D.; Korah, Reju; Carling, Tobias; Agrawal, Nishant; Cipriani, Nicole; Ball, Douglas; Nelkin, Barry; Rooper, Lisa M.; Bishop, Justin A.; Garnis, Cathie; Berean, Ken; Nicolson, Norman G.; Weinberger, Paul; Henderson, Ying C.; Lalansingh, Christopher M.; Tian, Mao; Yamaguchi, Takafumi N.; Livingstone, Julie; Salcedo, Adriana; Patel, Krupal; Vizeacoumar, Frederick; Datti, Alessandro; Xi, Liu; Nikiforov, Yuri E.; Smallridge, Robert; Copland, John A.; Marlow, Laura A.; Hyrcza, Martin D.; Delbridge, Leigh; Sidhu, Stan; Sywak, Mark; Robinson, Bruce; Fung, Kevin; Ghasemi, Farhad; Kwan, Keith; MacNeil, S. Danielle; Mendez, Adrian; Palma, David A.; Khan, Mohammed I.; Shaikh, Mushfiq; Ruicci, Kara M.; Wehrli, Bret; Winquist, Eric; Yoo, John; Mymryk, Joe S.; Rocco, James W.; Wheeler, David; Scherer, Steve; Giordano, Thomas J.; Barrett, John W.; Faquin, William C.; Gill, Anthony J.; Clayman, Gary; Boutros, Paul C.; Nichols, Anthony C.
Cell reports (Cambridge), 03/2024, Letnik: 43, Številka: 3Journal Article
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. Display omitted •Anaplastic thyroid carcinoma (ATC) is an aggressive cancer with poor treatment outcomes•Large-scale multi-region genomics identify distinct mutational processes•Subclonal reconstruction suggests ATC shares clonal origin with differentiated thyroid cancers Anaplastic thyroid cancer is one of the most lethal human cancers. Surprisingly, it often evolves alongside a highly non-lethal form of differentiated thyroid cancer. Zeng et al. demonstrate how these two diseases evolve from a common ancestor, leading to differential evolutionary trajectories and dramatic differences in clinical outcomes.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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