Repository logo
 

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Abbosh, C 
Birkbak, NJ 
Wilson, GA 
Jamal-Hanjani, M 
Constantin, T 

Abstract

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

Description

Keywords

Biopsy, Carcinoma, Non-Small-Cell Lung, Cell Lineage, Cell Tracking, Clone Cells, DNA Mutational Analysis, DNA, Neoplasm, Disease Progression, Drug Resistance, Neoplasm, Early Detection of Cancer, Evolution, Molecular, Humans, Limit of Detection, Lung Neoplasms, Multiplex Polymerase Chain Reaction, Neoplasm Metastasis, Neoplasm Recurrence, Local, Postoperative Care, Reproducibility of Results, Tumor Burden

Journal Title

Nature

Conference Name

Journal ISSN

0028-0836
1476-4687

Volume Title

545

Publisher

Nature Publishing Group