Phylogenetic ctDNA analysis depicts early stage lung cancer evolution
By C. Abbosh, Nicolai J. Birkbak, G. Wilson, M. Jamal-Hanjani, T. Constantin, R. Salari, J. Le Quesne, D. Moore, S. Veeriah, R. Rosenthal and 94 more. Nature, 2017
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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.
Subfields: Cancer Research, Pathology and Forensic Medicine, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/e1d0f0adcd7f7f3e0cacbbace93e4963e704101c
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In Cancer Research
In Pathology and Forensic Medicine
In Pulmonary and Respiratory Medicine
Citations in the corpus
- ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. (2022, background): “20,21 Several clinical and pathological factors are also associated with ctDNA levels.”
- Molecular profiling for precision cancer therapies (2020, background): “1Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Department of Medicine, University Avenue, University of Toronto, Toronto, Ontario M5G 1Z5, Canada Full list of author information is available at the end of the article Androgen receptor (AR) A”
- Circulating Tumor DNA Analysis in Patients With Cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. (2018, background): “Persistent detection of ctDNA after local therapy (surgery or radical radiotherapy) predicts for a high risk of relapse in proof-of-principle studies in colon cancer,(64,65,79) breast cancer,(80,81) pancreatic cancer,(82) and lung cancer.(83) In these studies, the primary tumor is often sequenced to”