Direct detection of early-stage cancers using circulating tumor DNA

Jillian Phallen, Mark Sausen, Vilmos Adleff, Alessandro Leal, Carolyn Hruban, James White, Valsamo Anagnostou, Jacob Fiksel, Stephen Cristiano, Eniko Papp, Savannah Speir, Thomas Reinert, Mai Britt Worm Orntoft, Brian D. Woodward, Derek Murphy, Sonya Parpart-Li, David Riley, Monica Nesselbush, Naomi Sengamalay, Andrew Georgiadis & 17 others Qing Kay Li, Mogens Rørbæk Madsen, Frank Viborg Mortensen, Joost Huiskens, Cornelis Punt, Nicole Van Grieken, Remond Fijneman, Gerrit Meijer, Hatim Husain, Robert B Scharpf, Luis A. Diaz, Sin Jones, Sam Angiuoli, Torben Ørntoft, Hans Jørgen Nielsen, Claus Lindbjerg Andersen, Victor E Velculescu

Research output: Contribution to journalArticle

Abstract

Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.

Original languageEnglish (US)
Article numbereaan2415
JournalScience Translational Medicine
Volume9
Issue number403
DOIs
StatePublished - Aug 16 2017

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Early Detection of Cancer
DNA
Neoplasms
High-Throughput Nucleotide Sequencing
Mutation
Neoplasm Genes
Hematopoiesis
Ovarian Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Breast Neoplasms
Morbidity
Recurrence
Survival
Mortality
Genes

ASJC Scopus subject areas

  • Medicine(all)

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Direct detection of early-stage cancers using circulating tumor DNA. / Phallen, Jillian; Sausen, Mark; Adleff, Vilmos; Leal, Alessandro; Hruban, Carolyn; White, James; Anagnostou, Valsamo; Fiksel, Jacob; Cristiano, Stephen; Papp, Eniko; Speir, Savannah; Reinert, Thomas; Orntoft, Mai Britt Worm; Woodward, Brian D.; Murphy, Derek; Parpart-Li, Sonya; Riley, David; Nesselbush, Monica; Sengamalay, Naomi; Georgiadis, Andrew; Li, Qing Kay; Madsen, Mogens Rørbæk; Mortensen, Frank Viborg; Huiskens, Joost; Punt, Cornelis; Van Grieken, Nicole; Fijneman, Remond; Meijer, Gerrit; Husain, Hatim; Scharpf, Robert B; Diaz, Luis A.; Jones, Sin; Angiuoli, Sam; Ørntoft, Torben; Nielsen, Hans Jørgen; Andersen, Claus Lindbjerg; Velculescu, Victor E.

In: Science Translational Medicine, Vol. 9, No. 403, eaan2415, 16.08.2017.

Research output: Contribution to journalArticle

Phallen, J, Sausen, M, Adleff, V, Leal, A, Hruban, C, White, J, Anagnostou, V, Fiksel, J, Cristiano, S, Papp, E, Speir, S, Reinert, T, Orntoft, MBW, Woodward, BD, Murphy, D, Parpart-Li, S, Riley, D, Nesselbush, M, Sengamalay, N, Georgiadis, A, Li, QK, Madsen, MR, Mortensen, FV, Huiskens, J, Punt, C, Van Grieken, N, Fijneman, R, Meijer, G, Husain, H, Scharpf, RB, Diaz, LA, Jones, S, Angiuoli, S, Ørntoft, T, Nielsen, HJ, Andersen, CL & Velculescu, VE 2017, 'Direct detection of early-stage cancers using circulating tumor DNA', Science Translational Medicine, vol. 9, no. 403, eaan2415. https://doi.org/10.1126/scitranslmed.aan2415
Phallen, Jillian ; Sausen, Mark ; Adleff, Vilmos ; Leal, Alessandro ; Hruban, Carolyn ; White, James ; Anagnostou, Valsamo ; Fiksel, Jacob ; Cristiano, Stephen ; Papp, Eniko ; Speir, Savannah ; Reinert, Thomas ; Orntoft, Mai Britt Worm ; Woodward, Brian D. ; Murphy, Derek ; Parpart-Li, Sonya ; Riley, David ; Nesselbush, Monica ; Sengamalay, Naomi ; Georgiadis, Andrew ; Li, Qing Kay ; Madsen, Mogens Rørbæk ; Mortensen, Frank Viborg ; Huiskens, Joost ; Punt, Cornelis ; Van Grieken, Nicole ; Fijneman, Remond ; Meijer, Gerrit ; Husain, Hatim ; Scharpf, Robert B ; Diaz, Luis A. ; Jones, Sin ; Angiuoli, Sam ; Ørntoft, Torben ; Nielsen, Hans Jørgen ; Andersen, Claus Lindbjerg ; Velculescu, Victor E. / Direct detection of early-stage cancers using circulating tumor DNA. In: Science Translational Medicine. 2017 ; Vol. 9, No. 403.
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AU - Phallen, Jillian

AU - Sausen, Mark

AU - Adleff, Vilmos

AU - Leal, Alessandro

AU - Hruban, Carolyn

AU - White, James

AU - Anagnostou, Valsamo

AU - Fiksel, Jacob

AU - Cristiano, Stephen

AU - Papp, Eniko

AU - Speir, Savannah

AU - Reinert, Thomas

AU - Orntoft, Mai Britt Worm

AU - Woodward, Brian D.

AU - Murphy, Derek

AU - Parpart-Li, Sonya

AU - Riley, David

AU - Nesselbush, Monica

AU - Sengamalay, Naomi

AU - Georgiadis, Andrew

AU - Li, Qing Kay

AU - Madsen, Mogens Rørbæk

AU - Mortensen, Frank Viborg

AU - Huiskens, Joost

AU - Punt, Cornelis

AU - Van Grieken, Nicole

AU - Fijneman, Remond

AU - Meijer, Gerrit

AU - Husain, Hatim

AU - Scharpf, Robert B

AU - Diaz, Luis A.

AU - Jones, Sin

AU - Angiuoli, Sam

AU - Ørntoft, Torben

AU - Nielsen, Hans Jørgen

AU - Andersen, Claus Lindbjerg

AU - Velculescu, Victor E

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