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Region Hovedstaden - en del af Københavns Universitetshospital
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Direct detection of early-stage cancers using circulating tumor DNA

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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  • Jillian Phallen
  • Mark Sausen
  • Vilmos Adleff
  • Alessandro Leal
  • Carolyn A Hruban
  • James R 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
  • Qing Kay Li
  • Mogens Rørbæk Madsen
  • Frank Viborg Mortensen
  • Joost Huiskens
  • Cornelis J A Punt
  • Nicole C T van Grieken
  • Remond J A Fijneman
  • Gerrit A Meijer
  • Hatim Husain
  • Robert B Scharpf
  • Luis A Diaz
  • Siân Jones
  • Sam Angiuoli
  • Torben Falck Ørntoft
  • Hans Jørgen Nielsen
  • Claus Lindbjerg Andersen
  • Victor E Velculescu
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftScience translational medicine
Vol/bind9
Udgave nummer403
ISSN1946-6234
DOI
StatusUdgivet - 1 aug. 2017

ID: 51564917