Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology.

Circulating Tumor DNA / genetics High-Throughput Nucleotide Sequencing / methods Humans Limit of Detection Medical Oncology Neoplasms / genetics Practice Guidelines as Topic Precision Medicine Reproducibility of Results Sequence Analysis, DNA / standards

Journal

Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648

Informations de publication

Date de publication:
09 2021
Historique:
received: 20 07 2020
accepted: 15 02 2021
pubmed: 14 4 2021
medline: 23 9 2021
entrez: 13 4 2021
Statut: ppublish

Résumé

Circulating tumor DNA (ctDNA) sequencing is being rapidly adopted in precision oncology, but the accuracy, sensitivity and reproducibility of ctDNA assays is poorly understood. Here we report the findings of a multi-site, cross-platform evaluation of the analytical performance of five industry-leading ctDNA assays. We evaluated each stage of the ctDNA sequencing workflow with simulations, synthetic DNA spike-in experiments and proficiency testing on standardized, cell-line-derived reference samples. Above 0.5% variant allele frequency, ctDNA mutations were detected with high sensitivity, precision and reproducibility by all five assays, whereas, below this limit, detection became unreliable and varied widely between assays, especially when input material was limited. Missed mutations (false negatives) were more common than erroneous candidates (false positives), indicating that the reliable sampling of rare ctDNA fragments is the key challenge for ctDNA assays. This comprehensive evaluation of the analytical performance of ctDNA assays serves to inform best practice guidelines and provides a resource for precision oncology.

Identifiants

DOI: 10.1038/s41587-021-00857-z PMID: 33846644 PMC: PMC8434938
pubmed: 33846644
doi: 10.1038/s41587-021-00857-z
pii: 10.1038/s41587-021-00857-z
pmc: PMC8434938
mid: NIHMS1674229
doi:

Substances chimiques

Circulating Tumor DNA 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

1115-1128

Subventions

Organisme : U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration)
ID : E0765001
Organisme : NIGMS NIH HHS
ID : R15 GM114739
Pays : United States
Organisme : U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration)
ID : E0767001
Organisme : Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission)
ID : 2017SHZDZX01
Organisme : NIGMS NIH HHS
ID : R15 GM137288
Pays : United States
Organisme : U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration)
ID : BAA grant HHSF223201510172C
Organisme : Intramural FDA HHS
ID : FD999999
Pays : United States
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : APP1108254
Organisme : Cancer Institute NSW (Cancer Institute New South Wales)
ID : Early Career Fellowship 2018/ECF013
Organisme : NIGMS NIH HHS
ID : P50 GM021700
Pays : United States

Informations de copyright

© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

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Auteurs

Ira W Deveson (IW)

Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia.
St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
ORCID: 0000-0003-3861-0472

Binsheng Gong (B)

Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.

Kevin Lai (K)

Bioinformatics, Integrated DNA Technologies, Inc., Coralville, IA, USA.

Jennifer S LoCoco (JS)

Illumina, Inc., San Diego, CA, USA.
ORCID: 0000-0002-7437-5177

Todd A Richmond (TA)

Market & Application Development Bioinformatics, Roche Sequencing Solutions Inc., Pleasanton, CA, USA.
ORCID: 0000-0003-1508-6540

Jeoffrey Schageman (J)

Clinical Sequencing Division, Thermo Fisher Scientific, Austin, TX, USA.

Zhihong Zhang (Z)

Research and Development, Burning Rock Biotech, Shanghai, China.

Natalia Novoradovskaya (N)

Agilent Technologies, La Jolla, CA, USA.

James C Willey (JC)

Departments of Medicine, Pathology, and Cancer Biology, College of Medicine and Life Sciences, University of Toledo Health Sciences Campus, Toledo, OH, USA.

Wendell Jones (W)

Q2 Solutions - EA Genomics, Morrisville, NC, USA.
ORCID: 0000-0002-9676-5387

Rebecca Kusko (R)

Immuneering Corporation, Cambridge, MA, USA.
ORCID: 0000-0001-6730-5990

Guangchun Chen (G)

Department of Immunology, Genomics and Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Bindu Swapna Madala (BS)

Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.

James Blackburn (J)

Cancer Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.
ORCID: 0000-0001-5216-8815

Igor Stevanovski (I)

Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia.

Ambica Bhandari (A)

ResearchDx, Inc., Irvine, CA, USA.

Devin Close (D)

R&D Genomics MPS, Institute for Clinical and Experimental Pathology ARUP Laboratories, Salt Lake City, UT, USA.

Jeffrey Conroy (J)

OmniSeq, Inc., Buffalo, NY, USA.

Michael Hubank (M)

NIHR Biomedical Research Centre, Royal Marsden Hospital, Sutton, Surrey, UK.

Narasimha Marella (N)

Cancer Genetics, Inc., Rutherford, NJ, USA.

Piotr A Mieczkowski (PA)

Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
ORCID: 0000-0003-2418-0096

Fujun Qiu (F)

Research and Development, Burning Rock Biotech, Shanghai, China.

Robert Sebra (R)

Icahn Institute and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Daniel Stetson (D)

Astrazeneca Pharmaceuticals, Waltham, MA, USA.

Lihyun Sun (L)

Elim Biopharmaceuticals, Inc., Hayward, CA, USA.

Philippe Szankasi (P)

R&D Genomics MPS, Institute for Clinical and Experimental Pathology ARUP Laboratories, Salt Lake City, UT, USA.

Haowen Tan (H)

Primbio Genes Biotechnology, East Lake High-tech Development Zone, Wuhan, Hubei, China.

Lin-Ya Tang (LY)

Institute for Personalized Cancer Therapy, MD Anderson Cancer Center, Houston, TX, USA.

Hanane Arib (H)

Icahn Institute and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Hunter Best (H)

R&D Genomics MPS, Institute for Clinical and Experimental Pathology ARUP Laboratories, Salt Lake City, UT, USA.
Departments of Pathology and Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.

Blake Burgher (B)

OmniSeq, Inc., Buffalo, NY, USA.

Pierre R Bushel (PR)

National Institute of Environmental Health Sciences, Research Triangle Park, Morrisville, NC, USA.

Fergal Casey (F)

Market & Application Development Bioinformatics, Roche Sequencing Solutions Inc., Pleasanton, CA, USA.

Simon Cawley (S)

Clinical Sequencing Division, Thermo Fisher Scientific, South San Francisco, CA, USA.

Chia-Jung Chang (CJ)

Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA.

Jonathan Choi (J)

Roche Sequencing Solutions, Inc., Pleasanton, CA, USA.

Jorge Dinis (J)

Roche Sequencing Solutions, Inc., Pleasanton, CA, USA.

Daniel Duncan (D)

Cancer Genetics, Inc., Rutherford, NJ, USA.

Agda Karina Eterovic (AK)

Institute for Personalized Cancer Therapy, MD Anderson Cancer Center, Houston, TX, USA.

Liang Feng (L)

Market & Application Development Bioinformatics, Roche Sequencing Solutions Inc., Pleasanton, CA, USA.

Abhisek Ghosal (A)

ResearchDx, Inc., Irvine, CA, USA.

Kristina Giorda (K)

Marketing, Integrated DNA Technologies, Inc., Coralville, IA, USA.

Sean Glenn (S)

OmniSeq, Inc., Buffalo, NY, USA.

Scott Happe (S)

Agilent Technologies, Cedar Creek, TX, USA.

Nathan Haseley (N)

Illumina, Inc., San Diego, CA, USA.

Kyle Horvath (K)

ResearchDx, Inc., Irvine, CA, USA.

Li-Yuan Hung (LY)

Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Mirna Jarosz (M)

NGS Products and Services, Integrated DNA Technologies, Inc., Coralville, IA, USA.

Garima Kushwaha (G)

Market & Application Development Bioinformatics, Roche Sequencing Solutions Inc., Pleasanton, CA, USA.

Dan Li (D)

Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
ORCID: 0000-0001-6394-7953

Quan-Zhen Li (QZ)

Department of Immunology, Genomics and Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Zhiguang Li (Z)

Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Liang-Chun Liu (LC)

Clinical Diagnostic Division, Thermo Fisher Scientific, Fremont, CA, USA.

Zhichao Liu (Z)

Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.

Charles Ma (C)

Cancer Genetics, Inc., Rutherford, NJ, USA.

Christopher E Mason (CE)

Department of Physiology and Biophysics, Weill Cornell Medicine, Cornell University, New York, NY, USA.
ORCID: 0000-0002-1850-1642

Dalila B Megherbi (DB)

CMINDS Research Center, Department of Electrical and Computer Engineering, College of Engineering, University of Massachusetts Lowell, Lowell, MA, USA.

Tom Morrison (T)

Accugenomics, Inc., Wilmington, NC, USA.

Carlos Pabón-Peña (C)

Agilent Technologies, Santa Clara, CA, USA.

Mehdi Pirooznia (M)

Bioinformatics and Computational Biology Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-4210-6458

Paula Z Proszek (PZ)

NIHR Biomedical Research Centre, Royal Marsden Hospital, Sutton, Surrey, UK.

Amelia Raymond (A)

Astrazeneca Pharmaceuticals, Waltham, MA, USA.

Paul Rindler (P)

R&D Genomics MPS, Institute for Clinical and Experimental Pathology ARUP Laboratories, Salt Lake City, UT, USA.

Rebecca Ringler (R)

ResearchDx, Inc., Irvine, CA, USA.

Andreas Scherer (A)

Institute for Molecular Medicine Finland (FIMM), Nordic EMBL Partnership for Molecular Medicine, HiLIFE Unit, Biomedicum Helsinki 2U (D302b), University of Helsinki, Helsinki, Finland.
EATRIS ERIC- European Infrastructure for Translational Medicine, Amsterdam, The Netherlands.
ORCID: 0000-0002-4254-7122

Rita Shaknovich (R)

Cancer Genetics, Inc., Rutherford, NJ, USA.

Tieliu Shi (T)

Center for Bioinformatics and Computational Biology and the Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China.

Melissa Smith (M)

Icahn Institute and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Ping Song (P)

Institute for Personalized Cancer Therapy, MD Anderson Cancer Center, Houston, TX, USA.

Maya Strahl (M)

Icahn Institute and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Venkat J Thodima (VJ)

Cancer Genetics, Inc., Rutherford, NJ, USA.

Nikola Tom (N)

EATRIS ERIC- European Infrastructure for Translational Medicine, Amsterdam, The Netherlands.
Center of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

Suman Verma (S)

ResearchDx, Inc., Irvine, CA, USA.

Jiashi Wang (J)

Research and Development, Integrated DNA Technologies, Inc., Coralville, IA, USA.

Leihong Wu (L)

Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.

Wenzhong Xiao (W)

Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA.
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Chang Xu (C)

Research and Development, QIAGEN Sciences, Inc., Frederick, MD, USA.

Mary Yang (M)

Department of Information Science, University of Arkansas at Little Rock, Little Rock, AR, USA.

Guangliang Zhang (G)

Clinical Laboratory, Burning Rock Biotech, Guangzhou, China.

Sa Zhang (S)

Clinical Laboratory, Burning Rock Biotech, Guangzhou, China.

Yilin Zhang (Y)

Elim Biopharmaceuticals, Inc., Hayward, CA, USA.

Leming Shi (L)

State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Hospital/Cancer Institute, Fudan University, Shanghai, China.
Human Phenome Institute, Fudan University, Shanghai, China.
Fudan-Gospel Joint Research Center for Precision Medicine, Fudan University, Shanghai, China.

Weida Tong (W)

Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.

Donald J Johann (DJ)

Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA. djjohann@uams.edu.

Timothy R Mercer (TR)

St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. t.mercer@garvan.org.au.
Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia. t.mercer@garvan.org.au.
Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Queensland, QLD, Australia. t.mercer@garvan.org.au.
ORCID: 0000-0001-8780-894X

Joshua Xu (J)

Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA. joshua.xu@fda.hhs.gov.
ORCID: 0000-0001-5313-5847

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Classifications MeSH

questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN tumoral › ADN tumoral circulant › Evaluating the analytical validity of...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Séquençage nucléotidique à haut débit › Evaluating the analytical validity of...
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