Cell Reports (Mar 2024)
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
Affiliations
- Peter Y.F. Zeng
- 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
- Stephenie D. Prokopec
- 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
- Stephen Y. Lai
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Nicole Pinto
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada
- Michelle A. Chan-Seng-Yue
- Ontario Institute for Cancer Research, Toronto, ON, Canada
- Roderick Clifton-Bligh
- Division of Endocrinology, Royal North Shore Hospital, and University of Sydney, Sydney, NSW, Australia
- Michelle D. Williams
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Christopher J. Howlett
- Department of Pathology, Western University, London, ON, Canada
- Paul Plantinga
- Department of Pathology, Western University, London, ON, Canada
- Matthew J. Cecchini
- Department of Pathology, School of Medicine, Griffith University, Gold Coast, QLD, Australia
- Alfred K. Lam
- Department of Pathology, School of Medicine, Griffith University, Gold Coast, QLD, Australia
- Iram Siddiqui
- Department of Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada
- Jianxin Wang
- Ontario Institute for Cancer Research, Toronto, ON, Canada
- Ren X. Sun
- Ontario Institute for Cancer Research, Toronto, ON, Canada
- John D. Watson
- 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
- Reju Korah
- Department of Surgery, Yale University, New Haven, CT, USA
- Tobias Carling
- Department of Surgery, Yale University, New Haven, CT, USA
- Nishant Agrawal
- Department of Otolaryngology – Head and Neck Surgery, University of Chicago, Chicago, IL, USA
- Nicole Cipriani
- Department of Pathology, University of Chicago, Chicago, IL, USA
- Douglas Ball
- Division of Endocrinology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
- Barry Nelkin
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
- Lisa M. Rooper
- Division of Pathology, Johns Hopkins University, Baltimore, MD, USA
- Justin A. Bishop
- Department of Pathology, University of Texas Southwestern, Dallas, TX, USA
- Cathie Garnis
- BC Cancer Agency, Vancouver, BC, Canada
- Ken Berean
- BC Cancer Agency, Vancouver, BC, Canada
- Norman G. Nicolson
- Department of Surgery, Yale University, New Haven, CT, USA
- Paul Weinberger
- 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
- Ying C. Henderson
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Christopher M. Lalansingh
- Ontario Institute for Cancer Research, Toronto, ON, Canada
- Mao Tian
- 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
- Takafumi N. Yamaguchi
- 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
- Julie Livingstone
- 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
- Adriana Salcedo
- 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
- Krupal Patel
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada
- Frederick Vizeacoumar
- Cancer Research Cluster, University of Saskatchewan, Saskatoon, SK, Canada
- Alessandro Datti
- 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
- Liu Xi
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
- Yuri E. Nikiforov
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Robert Smallridge
- Division of Endocrinology, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA
- John A. Copland
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA
- Laura A. Marlow
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA
- Martin D. Hyrcza
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
- Leigh Delbridge
- Department of Surgery, Royal North Shore Hospital, Sydney, NSW, Australia; University of Sydney, Sydney, NWS, Australia
- Stan Sidhu
- Department of Surgery, Royal North Shore Hospital, Sydney, NSW, Australia; University of Sydney, Sydney, NWS, Australia
- Mark Sywak
- Department of Surgery, Royal North Shore Hospital, Sydney, NSW, Australia; University of Sydney, Sydney, NWS, Australia
- Bruce Robinson
- University of Sydney, Sydney, NWS, Australia; Department of Endocrinology, Royal North Shore Hospital, Sydney, NSW, Australia
- Kevin Fung
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada
- Farhad Ghasemi
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada
- Keith Kwan
- Department of Pathology, Western University, London, ON, Canada
- S. Danielle MacNeil
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada
- Adrian Mendez
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada
- David A. Palma
- London Regional Cancer Program, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada
- Mohammed I. Khan
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada
- Mushfiq Shaikh
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada
- Kara M. Ruicci
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada
- Bret Wehrli
- Department of Pathology, Western University, London, ON, Canada
- Eric Winquist
- London Regional Cancer Program, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada
- John Yoo
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada
- Joe S. Mymryk
- 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
- James W. Rocco
- Department of Otolaryngology – Head and Neck Surgery, Ohio State University, Columbus, OH, USA
- David Wheeler
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
- Steve Scherer
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
- Thomas J. Giordano
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
- John W. Barrett
- Department of Otolaryngology – Head and Neck Surgery, Western University, London, ON, Canada
- William C. Faquin
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Anthony J. Gill
- 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
- Gary Clayman
- The Clayman Thyroid Surgery and Thyroid Cancer Center, The Thyroid Institute, Tampa General Hospital, Tampa, FL, USA
- Paul C. Boutros
- 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; Corresponding author
- Anthony C. Nichols
- 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; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 3
p. 113826
Abstract
Summary: 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.
