Detection and characterization of lung cancer using cell-free DNA fragmentomes

Dimitrios Mathios, Jakob Sidenius Johansen, Stephen Cristiano, Jamie E. Medina, Jillian Phallen, Klaus R. Larsen, Daniel C. Bruhm, Noushin Niknafs, Leonardo Ferreira, Vilmos Adleff, Jia Yuee Chiao, Alessandro Leal, Michael Noe, James R. White, Adith S. Arun, Carolyn Hruban, Akshaya V. Annapragada, Sarah Østrup Jensen, Mai-Britt Worm Ørntoft, Anders Husted Madsen, Beatriz Carvalho, Meike Wit, Jacob Carey, Nicholas C. Dracopoli, Tara Maddala, Kenneth C. Fang, Anne-Renee Hartman, Patrick M. Forde, Valsamo Anagnostou, Julie R. Brahmer, Remond J. A. Fijneman, Hans Jørgen Nielsen, Gerrit A. Meijer, Claus Lindbjerg Andersen, Anders Mellemgaard, Stig E. Bojesen, Robert B. Scharpf () and Victor E. Velculescu ()
Additional contact information
Dimitrios Mathios: Johns Hopkins University School of Medicine
Jakob Sidenius Johansen: Herlev and Gentofte Hospital
Stephen Cristiano: Johns Hopkins University School of Medicine
Jamie E. Medina: Johns Hopkins University School of Medicine
Jillian Phallen: Johns Hopkins University School of Medicine
Klaus R. Larsen: Infiltrate Unit, Bispebjerg Hospital
Daniel C. Bruhm: Johns Hopkins University School of Medicine
Noushin Niknafs: Johns Hopkins University School of Medicine
Leonardo Ferreira: Johns Hopkins University School of Medicine
Vilmos Adleff: Johns Hopkins University School of Medicine
Jia Yuee Chiao: Johns Hopkins University School of Medicine
Alessandro Leal: Johns Hopkins University School of Medicine
Michael Noe: Johns Hopkins University School of Medicine
James R. White: Johns Hopkins University School of Medicine
Adith S. Arun: Johns Hopkins University School of Medicine
Carolyn Hruban: Johns Hopkins University School of Medicine
Akshaya V. Annapragada: Johns Hopkins University School of Medicine
Sarah Østrup Jensen: Aarhus University Hospital
Mai-Britt Worm Ørntoft: Aarhus University Hospital
Anders Husted Madsen: Herning Regional Hospital
Beatriz Carvalho: The Netherlands Cancer Institute
Meike Wit: The Netherlands Cancer Institute
Jacob Carey: Delfi Diagnostics
Nicholas C. Dracopoli: Delfi Diagnostics
Tara Maddala: Delfi Diagnostics
Kenneth C. Fang: Delfi Diagnostics
Anne-Renee Hartman: Delfi Diagnostics
Patrick M. Forde: Johns Hopkins University School of Medicine
Valsamo Anagnostou: Johns Hopkins University School of Medicine
Julie R. Brahmer: Johns Hopkins University School of Medicine
Remond J. A. Fijneman: The Netherlands Cancer Institute
Hans Jørgen Nielsen: Hvidovre Hospital
Gerrit A. Meijer: The Netherlands Cancer Institute
Claus Lindbjerg Andersen: Herning Regional Hospital
Anders Mellemgaard: Herlev and Gentofte Hospital
Stig E. Bojesen: Herlev and Gentofte Hospital
Robert B. Scharpf: Johns Hopkins University School of Medicine
Victor E. Velculescu: Johns Hopkins University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients. Combining fragmentation features, clinical risk factors, and CEA levels, followed by CT imaging, detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites distinguished individuals with small cell lung cancer from those with non-small cell lung cancer with high accuracy (AUC = 0.98). A higher fragmentation score represented an independent prognostic indicator of survival. This approach provides a facile avenue for non-invasive detection of lung cancer.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (8)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24994-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24994-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24994-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().