Author:
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,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.
Abstract
AbstractAnaplastic 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 and multi-region whole-genome sequencing. Anaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Specific cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. 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.
Publisher
Cold Spring Harbor Laboratory