The genomic and evolutionary landscapes of anaplastic thyroid carcinoma

Peter Y F Zeng; Stephenie D Prokopec; Stephen Y Lai; Nicole Pinto; Michelle A 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 X Sun; John D Watson; Reju Korah; Tobias Carling; Nishant Agrawal; Nicole Cipriani; Douglas Ball; Barry 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 Vizeacoumar; Alessandro Datti; Liu Xi; Yuri E Nikiforov; Robert Smallridge; John A Copland; Laura A Marlow; Martin D Hyrcza; Leigh Delbridge; Stan Sidhu; Mark Sywak; Bruce Robinson; Kevin Fung; Farhad Ghasemi; Keith Kwan; S Danielle MacNeil; Adrian Mendez; David A Palma; Mohammed I Khan; Mushfiq Shaikh; Kara M Ruicci; Bret Wehrli; Eric Winquist; John Yoo; Joe S Mymryk; James W Rocco; David Wheeler; Steve Scherer; Thomas J Giordano; John W Barrett; William C Faquin; Anthony J Gill; Gary Clayman; Paul C Boutros; Anthony C Nichols

doi:10.1016/j.celrep.2024.113826

The genomic and evolutionary landscapes of anaplastic thyroid carcinoma

Cell Rep. 2024 Mar 26;43(3):113826. doi: 10.1016/j.celrep.2024.113826. Epub 2024 Feb 26.

Authors

Peter Y F Zeng¹, Stephenie D Prokopec², Stephen Y Lai³, Nicole Pinto⁴, Michelle A Chan-Seng-Yue⁵, Roderick Clifton-Bligh⁶, Michelle D Williams⁷, Christopher J Howlett⁸, Paul Plantinga⁸, Matthew J Cecchini⁹, Alfred K Lam⁹, Iram Siddiqui¹⁰, Jianxin Wang⁵, Ren X Sun⁵, John D Watson², Reju Korah¹¹, Tobias Carling¹¹, Nishant Agrawal¹², Nicole Cipriani¹³, Douglas Ball¹⁴, Barry Nelkin¹⁵, Lisa M Rooper¹⁶, Justin A Bishop¹⁷, Cathie Garnis¹⁸, Ken Berean¹⁸, Norman G Nicolson¹¹, Paul Weinberger¹⁹, Ying C Henderson³, Christopher M Lalansingh⁵, Mao Tian²⁰, Takafumi N Yamaguchi², Julie Livingstone², Adriana Salcedo²¹, Krupal Patel²², Frederick Vizeacoumar²³, Alessandro Datti²⁴, Liu Xi²⁵, Yuri E Nikiforov²⁶, Robert Smallridge²⁷, John A Copland²⁸, Laura A Marlow²⁸, Martin D Hyrcza²⁹, Leigh Delbridge³⁰, Stan Sidhu³⁰, Mark Sywak³⁰, Bruce Robinson³¹, Kevin Fung³², Farhad Ghasemi⁴, Keith Kwan⁸, S Danielle MacNeil³², Adrian Mendez³², David A Palma³³, Mohammed I Khan⁴, Mushfiq Shaikh⁴, Kara M Ruicci⁴, Bret Wehrli⁸, Eric Winquist³³, John Yoo³², Joe S Mymryk³⁴, James W Rocco³⁵, David Wheeler²⁵, Steve Scherer²⁵, Thomas J Giordano³⁶, John W Barrett⁴, William C Faquin³⁷, Anthony J Gill³⁸, Gary Clayman³⁹, Paul C Boutros⁴⁰, Anthony C Nichols⁴¹

Affiliations

¹ 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.
² 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.
³ Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Department of Otolaryngology - Head and Neck Surgery, Western University, London, ON, Canada.
⁵ Ontario Institute for Cancer Research, Toronto, ON, Canada.
⁶ Division of Endocrinology, Royal North Shore Hospital, and University of Sydney, Sydney, NSW, Australia.
⁷ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Pathology, Western University, London, ON, Canada.
⁹ Department of Pathology, School of Medicine, Griffith University, Gold Coast, QLD, Australia.
¹⁰ Department of Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada.
¹¹ Department of Surgery, Yale University, New Haven, CT, USA.
¹² Department of Otolaryngology - Head and Neck Surgery, University of Chicago, Chicago, IL, USA.
¹³ Department of Pathology, University of Chicago, Chicago, IL, USA.
¹⁴ Division of Endocrinology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
¹⁵ Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
¹⁶ Division of Pathology, Johns Hopkins University, Baltimore, MD, USA.
¹⁷ Department of Pathology, University of Texas Southwestern, Dallas, TX, USA.
¹⁸ BC Cancer Agency, Vancouver, BC, Canada.
¹⁹ Department of Otolaryngology - Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
²⁰ 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.
²¹ Ontario Institute for Cancer Research, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
²² Department of Otolaryngology - Head and Neck Surgery, Western University, London, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada.
²³ Cancer Research Cluster, University of Saskatchewan, Saskatoon, SK, Canada.
²⁴ Network Biology Collaborative Centre, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Department of Agricultural, Food, and Environmental Sciences, University of Perugia, Perugia, Italy.
²⁵ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
²⁶ Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
²⁷ Division of Endocrinology, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA.
²⁸ Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA.
²⁹ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
³⁰ Department of Surgery, Royal North Shore Hospital, Sydney, NSW, Australia; University of Sydney, Sydney, NWS, Australia.
³¹ University of Sydney, Sydney, NWS, Australia; Department of Endocrinology, Royal North Shore Hospital, Sydney, NSW, Australia.
³² Department of Otolaryngology - Head and Neck Surgery, Western University, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada.
³³ London Regional Cancer Program, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada.
³⁴ Department of Otolaryngology - Head and Neck Surgery, Western University, London, ON, Canada; London Regional Cancer Program, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada; Department of Microbiology and Immunology, Western University, London, ON, Canada.
³⁵ Department of Otolaryngology - Head and Neck Surgery, Ohio State University, Columbus, OH, USA.
³⁶ Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
³⁷ Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
³⁸ University of Sydney, Sydney, NWS, Australia; Cancer Diagnosis and Pathology Group, Kolling Institute of Medicine, Royal North Shore Hospital, Sydney, NSW, Australia; NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia.
³⁹ The Clayman Thyroid Surgery and Thyroid Cancer Center, The Thyroid Institute, Tampa General Hospital, Tampa, FL, USA.
⁴⁰ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; 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. Electronic address: pboutros@mednet.ucla.edu.
⁴¹ 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. Electronic address: anthony.nichols@lhsc.on.ca.

PMID: 38412093
DOI: 10.1016/j.celrep.2024.113826

Abstract

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.

Keywords: CP: Cancer; CP: Genomics; anaplastic thyroid cancer; cancer progression; genomics; tumour evolution; tumour heterogeneity.

MeSH terms

Adenocarcinoma*
Genomics
Humans
Mutation / genetics
Thyroid Carcinoma, Anaplastic* / genetics
Thyroid Carcinoma, Anaplastic* / pathology
Thyroid Neoplasms* / genetics
Thyroid Neoplasms* / pathology

Grants and funding

U24 CA248265/CA/NCI NIH HHS/United States