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Nature Research, Nature, 7655(545), p. 446-451, 2017

DOI: 10.1038/nature22364

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Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

Journal article published in 2017 by Colin Watts, Gareth A. Wilson, Rodelaine Wilson, Thomas B. K. Watkins, Francisco Zambrana, Henning Walczak, Sophia Ward, Marafioti Teresa, Anne Marie Quinn, Richard Kevin Stone, Raymondo Endozo, Eva Gronroos, David A. Moore, Fiona M. Fennessy, Diana Johnson and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies.