Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA.

Biomarkers, Tumor / genetics Circulating Tumor DNA / genetics High-Throughput Nucleotide Sequencing / methods Humans Mutation / genetics Neoplasm, Residual / diagnosis

Journal

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

Informations de publication

Date de publication:
12 2021
Historique:
received: 14 03 2020
accepted: 11 06 2021
pubmed: 24 7 2021
medline: 20 4 2022
entrez: 23 7 2021
Statut: ppublish

Résumé

Circulating tumor-derived DNA (ctDNA) is an emerging biomarker for many cancers, but the limited sensitivity of current detection methods reduces its utility for diagnosing minimal residual disease. Here we describe phased variant enrichment and detection sequencing (PhasED-seq), a method that uses multiple somatic mutations in individual DNA fragments to improve the sensitivity of ctDNA detection. Leveraging whole-genome sequences from 2,538 tumors, we identify phased variants and their associations with mutational signatures. We show that even without molecular barcodes, the limits of detection of PhasED-seq outperform prior methods, including duplex barcoding, allowing ctDNA detection in the ppm range in participant samples. We profiled 678 specimens from 213 participants with B cell lymphomas, including serial cell-free DNA samples before and during therapy for diffuse large B cell lymphoma. In participants with undetectable ctDNA after two cycles of therapy using a next-generation sequencing-based approach termed cancer personalized profiling by deep sequencing, an additional 25% have ctDNA detectable by PhasED-seq and have worse outcomes. Finally, we demonstrate the application of PhasED-seq to solid tumors.

Identifiants

DOI: 10.1038/s41587-021-00981-w PMID: 34294911 PMC: PMC8678141
pubmed: 34294911
doi: 10.1038/s41587-021-00981-w
pii: 10.1038/s41587-021-00981-w
pmc: PMC8678141
mid: NIHMS1714594
doi:

Substances chimiques

Biomarkers, Tumor 0
Circulating Tumor DNA 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1537-1547

Subventions

Organisme : NCI NIH HHS
ID : R01 CA254179
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009302
Pays : United States
Organisme : NCI NIH HHS
ID : R43 CA199142
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229766
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA194389
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA233975
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA244526
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA241076
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA188298
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA257655
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

David M Kurtz (DM)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
ORCID: 0000-0002-6382-4651

Joanne Soo (J)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.

Lyron Co Ting Keh (L)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.

Stefan Alig (S)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
ORCID: 0000-0001-6825-702X

Jacob J Chabon (JJ)

Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
Foresight Diagnostics, Aurora, CO, USA.
ORCID: 0000-0003-1820-9737

Brian J Sworder (BJ)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.

Andre Schultz (A)

Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
ORCID: 0000-0002-2909-3154

Michael C Jin (MC)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.

Florian Scherer (F)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
ORCID: 0000-0001-9635-5487

Andrea Garofalo (A)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.

Charles W Macaulay (CW)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.

Emily G Hamilton (EG)

Program in Cancer Biology, Stanford University, Stanford, CA, USA.

Binbin Chen (B)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Department of Genetics, Stanford University, Stanford, CA, USA.
ORCID: 0000-0003-2973-2718

Mari Olsen (M)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.

Joseph G Schroers-Martin (JG)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Division of Hematology, Department of Medicine, Stanford University, Stanford, CA, USA.
ORCID: 0000-0003-4128-2537

Alexander F M Craig (AFM)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.

Everett J Moding (EJ)

Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
ORCID: 0000-0001-7913-5351

Mohammad S Esfahani (MS)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.

Chih Long Liu (CL)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.

Ulrich Dührsen (U)

Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, Essen, Germany.
ORCID: 0000-0002-4034-9472

Andreas Hüttmann (A)

Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, Essen, Germany.
ORCID: 0000-0003-2230-3873

René-Olivier Casasnovas (RO)

Department of Hematology, Hopital F. Mitterrand, CHU Dijon and INSERM, Dijon, France.
ORCID: 0000-0002-1156-8983

Jason R Westin (JR)

Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-1824-2337

Mark Roschewski (M)

Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0003-0278-2635

Wyndham H Wilson (WH)

Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Gianluca Gaidano (G)

Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.
ORCID: 0000-0002-4681-0151

Davide Rossi (D)

Hematology, Oncology Institute of Southern Switzerland and Institute of Oncology Research, Bellinzona, Switzerland.

Maximilian Diehn (M)

Stanford Cancer Institute, Stanford University, Stanford, CA, USA. diehn@stanford.edu.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA. diehn@stanford.edu.
Department of Radiation Oncology, Stanford University, Stanford, CA, USA. diehn@stanford.edu.
ORCID: 0000-0003-2032-0581

Ash A Alizadeh (AA)

Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA. arasha@stanford.edu.
Stanford Cancer Institute, Stanford University, Stanford, CA, USA. arasha@stanford.edu.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA. arasha@stanford.edu.
Division of Hematology, Department of Medicine, Stanford University, Stanford, CA, USA. arasha@stanford.edu.
ORCID: 0000-0002-5153-5625

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Enhanced detection of minimal residual disease...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN tumoral › ADN tumoral circulant › Enhanced detection of minimal residual disease...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Séquençage nucléotidique à haut débit › Enhanced detection of minimal residual disease...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Enhanced detection of minimal residual disease...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Enhanced detection of minimal residual disease...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Maladie résiduelle › Enhanced detection of minimal residual disease...