Evidence map›Paper›PMID 31768066›Full record

Trial reportNature medicine2019

High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants.

Pedram Razavi, Bob T Li, David N Brown, Byoungsok Jung, Earl Hubbell, Ronglai Shen, Wassim Abida, Krishna Juluru, Ino De Bruijn, Chenlu Hou and 33 more

Abstract readClinical Trial
In one paragraph

Trial report in Nature medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 461 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
461citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

461 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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401 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors.

Pedram Razavi *Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. razavip@mskcc.org.ORCID http://orcid.org/0000-0003-4236-0576
Bob T Li *Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0001-6661-8733
David N Brown *Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Byoungsok JungGRAIL, Inc., Menlo Park, CA, USA.
Earl HubbellGRAIL, Inc., Menlo Park, CA, USA.
Ronglai ShenDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Wassim AbidaDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Krishna JuluruDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-8203-8894
Ino De BruijnMarie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-5427-4750
Chenlu HouGRAIL, Inc., Menlo Park, CA, USA.
Oliver VennGRAIL, Inc., Menlo Park, CA, USA.
Raymond LimDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Aseem AnandDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Tara MaddalaGRAIL, Inc., Menlo Park, CA, USA.
Sante GnerreGRAIL, Inc., Menlo Park, CA, USA.
Ravi Vijaya SatyaGRAIL, Inc., Menlo Park, CA, USA.
Qinwen LiuGRAIL, Inc., Menlo Park, CA, USA.
Ling ShenGRAIL, Inc., Menlo Park, CA, USA.
Nicholas EattockGRAIL, Inc., Menlo Park, CA, USA.
Jeanne YueGRAIL, Inc., Menlo Park, CA, USA.
Alexander W BlockerGRAIL, Inc., Menlo Park, CA, USA.ORCID http://orcid.org/0000-0002-7486-9919
Mark LeeGRAIL, Inc., Menlo Park, CA, USA.
Amy SehnertGRAIL, Inc., Menlo Park, CA, USA.
Hui XuGRAIL, Inc., Menlo Park, CA, USA.
Megan P HallGRAIL, Inc., Menlo Park, CA, USA.ORCID http://orcid.org/0000-0002-7300-5027
Angie Santiago-ZayasDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
William F NovotnyGRAIL, Inc., Menlo Park, CA, USA.
James M IsbellDepartment of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Valerie W RuschDepartment of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
George PlitasDepartment of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Alexandra S HeerdtDepartment of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Marc LadanyiDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
David M HymanDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0001-8150-9762
David R JonesDepartment of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Monica MorrowDepartment of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0003-4636-8313
Gregory J RielyDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Howard I ScherDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
Charles M RudinDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0001-5204-3465
Mark E RobsonDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0002-3109-1692
Luis A DiazDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0002-7079-8914
David B SolitDepartment of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.ORCID http://orcid.org/0000-0002-6614-802X
Alexander M AravanisGRAIL, Inc., Menlo Park, CA, USA.
Jorge S Reis-FilhoHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. reisfilj@mskcc.org.ORCID http://orcid.org/0000-0003-2969-3173

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
SPORE In Prostate CancerP50CA092629 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI JAMES A EASTHAM · 2001 to 2026
$63.0M
BRMS1-mediated suppression of metastases in p53 mutant lung adenocarcinomaR01CA217169 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI JONES, DAVID R · 2018 to 2022
$2.5M
Defining mechanisms of resistance to hormonal therapy in breast cancerR01CA234361 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CHANDARLAPATY, SARAT, SOLIT, DAVID B. · 2019 to 2023
$2.0M
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA092629NCI NIH HHS R01 CA217169NCI NIH HHS R01 CA234361
6 · The paper itself

Abstract

Accurate identification of tumor-derived somatic variants in plasma circulating cell-free DNA (cfDNA) requires understanding of the various biological compartments contributing to the cfDNA pool. We sought to define the technical feasibility of a high-intensity sequencing assay of cfDNA and matched white blood cell DNA covering a large genomic region (508 genes; 2 megabases; >60,000× raw depth) in a prospective study of 124 patients with metastatic cancer, with contemporaneous matched tumor tissue biopsies, and 47 controls without cancer. The assay displayed high sensitivity and specificity, allowing for de novo detection of tumor-derived mutations and inference of tumor mutational burden, microsatellite instability, mutational signatures and sources of somatic mutations identified in cfDNA. The vast majority of cfDNA mutations (81.6% in controls and 53.2% in patients with cancer) had features consistent with clonal hematopoiesis. This cfDNA sequencing approach revealed that clonal hematopoiesis constitutes a pervasive biological phenomenon, emphasizing the importance of matched cfDNA-white blood cell sequencing for accurate variant interpretation.

Indexed as

GenomicsAdultBiomarkers, TumorCell-Free Nucleic AcidsCirculating Tumor DNADNA Mutational AnalysisDNA, NeoplasmFemaleGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansMaleMicrosatellite InstabilityMiddle AgedMutationNeoplasmsBiomarkers, TumorCell-Free Nucleic AcidsCirculating Tumor DNADNA, Neoplasm

Identifiers

PMID31768066
PMCPMC7061455

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.