Journal article
Phylogenetic ctDNA analysis depicts early stage lung cancer evolution
CRUK Lung Cancer Centre of Excellence1
University Hospital of South Manchester2
Birmingham Heartlands Hospital3
University of Birmingham4
University of Aberdeen School of Medicine and Dentistry5
Leicester University Hospitals6
North Middlesex Hospital7
Royal Free Hospital8
The Princess Alexandra Hospital NHS Trust9
Royal Surrey County Hospital NHS Foundation Trust10
Ashford and St. Peters' Hospital11
Natera, Inc12
Velindre Hospital13
University Hospital Llandough14
University Hospital of Wales15
University College London16
Whittington Health NHS Trust17
Department of Bio and Health Informatics, Technical University of Denmark18
Cancer Genomics, Department of Bio and Health Informatics, Technical University of Denmark19
Max Delbrück Center for Molecular Medicine in the Helmholtz Association20
University of Leicester21
University College London Hospitals NHS Foundation Trust22
The Francis Crick Institute23
University College Hospital London24
Massachusetts General Hospital/Harvard Medical School25
University of Manchester26
Christie Hospital27
...and 17 moreThe 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.
| Language: | English |
|---|---|
| Publisher: | Nature Publishing Group UK |
| Year: | 2017 |
| Pages: | 446-451 |
| Journal subtitle: | International Weekly Journal of Science |
| ISSN: | 14764687 and 00280836 |
| Types: | Journal article |
| DOI: | 10.1038/nature22364 |
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
