Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Christopher Abbosh; Nicolai J Birkbak; Gareth A Wilson; Mariam Jamal-Hanjani; Tudor Constantin; Raheleh Salari; John Le Quesne; David A Moore; Selvaraju Veeriah; Rachel Rosenthal; Teresa Marafioti; Eser Kirkizlar; Thomas B K Watkins; Nicholas McGranahan; Sophia Ward; Luke Martinson; Joan Riley; Francesco Fraioli; Maise Al Bakir; Eva Grönroos; Francisco Zambrana; Raymondo Endozo; Wenya Linda Bi; Fiona M Fennessy; Nicole Sponer; Diana Johnson; Joanne Laycock; Seema Shafi; Justyna Czyzewska-Khan; Andrew Rowan; Tim Chambers; Nik Matthews; Samra Turajlic; Crispin Hiley; Siow Ming Lee; Martin D Forster; Tanya Ahmad; Mary Falzon; Elaine Borg; David Lawrence; Martin Hayward; Shyam Kolvekar; Nikolaos Panagiotopoulos; Sam M Janes; Ricky Thakrar; Asia Ahmed; Fiona Blackhall; Yvonne Summers; Dina Hafez; Gary Middleton; TRACERx consortium

doi:10.1038/nature22364

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Christopher Abbosh, Nicolai J Birkbak, Gareth A Wilson, Mariam Jamal-Hanjani, Tudor Constantin, Raheleh Salari, John Le Quesne, David A Moore, Selvaraju Veeriah, Rachel Rosenthal, Teresa Marafioti, Eser Kirkizlar, Thomas B K Watkins, Nicholas McGranahan, Sophia Ward, Luke Martinson, Joan Riley, Francesco Fraioli, Maise Al Bakir, Eva GrönroosFrancisco Zambrana, Raymondo Endozo, Wenya Linda Bi, Fiona M Fennessy, Nicole Sponer, Diana Johnson, Joanne Laycock, Seema Shafi, Justyna Czyzewska-Khan, Andrew Rowan, Tim Chambers, Nik Matthews, Samra Turajlic, Crispin Hiley, Siow Ming Lee, Martin D Forster, Tanya Ahmad, Mary Falzon, Elaine Borg, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Dina Hafez, Gary Middleton, TRACERx consortium

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

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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, 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.

Original language	English
Pages (from-to)	446-451
Number of pages	6
Journal	Nature
Volume	545
Issue number	7655
Early online date	26 Apr 2017
DOIs	https://doi.org/10.1038/nature22364
Publication status	Published - 25 May 2017

Keywords

Non-small-cell lung cancer
Tumour heterogeneity
Metastasis
Diagnostic markers
Predictive markers

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Abbosh_Naidu_Phylogenetic_ctDNA_analysis_Nature_2017
Eligibility for repository: Checked on 26/6/2017
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Abbosh, C., Birkbak, N. J., Wilson, G. A., Jamal-Hanjani, M., Constantin, T., Salari, R., Le Quesne, J., Moore, D. A., Veeriah, S., Rosenthal, R., Marafioti, T., Kirkizlar, E., Watkins, T. B. K., McGranahan, N., Ward, S., Martinson, L., Riley, J., Fraioli, F., Al Bakir, M., ... TRACERx consortium (2017). Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature, 545(7655), 446-451. https://doi.org/10.1038/nature22364

@article{546fedcd9d374f829636e77e602b3aac,

title = "Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution",

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.",

keywords = "Non-small-cell lung cancer, Tumour heterogeneity, Metastasis , Diagnostic markers, Predictive markers",

author = "Christopher Abbosh and Birkbak, {Nicolai J} and Wilson, {Gareth A} and Mariam Jamal-Hanjani and Tudor Constantin and Raheleh Salari and {Le Quesne}, John and Moore, {David A} and Selvaraju Veeriah and Rachel Rosenthal and Teresa Marafioti and Eser Kirkizlar and Watkins, {Thomas B K} and Nicholas McGranahan and Sophia Ward and Luke Martinson and Joan Riley and Francesco Fraioli and {Al Bakir}, Maise and Eva Gr{\"o}nroos and Francisco Zambrana and Raymondo Endozo and Bi, {Wenya Linda} and Fennessy, {Fiona M} and Nicole Sponer and Diana Johnson and Joanne Laycock and Seema Shafi and Justyna Czyzewska-Khan and Andrew Rowan and Tim Chambers and Nik Matthews and Samra Turajlic and Crispin Hiley and Lee, {Siow Ming} and Forster, {Martin D} and Tanya Ahmad and Mary Falzon and Elaine Borg and David Lawrence and Martin Hayward and Shyam Kolvekar and Nikolaos Panagiotopoulos and Janes, {Sam M} and Ricky Thakrar and Asia Ahmed and Fiona Blackhall and Yvonne Summers and Dina Hafez and Gary Middleton and {TRACERx consortium}",

year = "2017",

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doi = "10.1038/nature22364",

language = "English",

volume = "545",

pages = "446--451",

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Abbosh, C, Birkbak, NJ, Wilson, GA, Jamal-Hanjani, M, Constantin, T, Salari, R, Le Quesne, J, Moore, DA, Veeriah, S, Rosenthal, R, Marafioti, T, Kirkizlar, E, Watkins, TBK, McGranahan, N, Ward, S, Martinson, L, Riley, J, Fraioli, F, Al Bakir, M, Grönroos, E, Zambrana, F, Endozo, R, Bi, WL, Fennessy, FM, Sponer, N, Johnson, D, Laycock, J, Shafi, S, Czyzewska-Khan, J, Rowan, A, Chambers, T, Matthews, N, Turajlic, S, Hiley, C, Lee, SM, Forster, MD, Ahmad, T, Falzon, M, Borg, E, Lawrence, D, Hayward, M, Kolvekar, S, Panagiotopoulos, N, Janes, SM, Thakrar, R, Ahmed, A, Blackhall, F, Summers, Y, Hafez, D, Middleton, G & TRACERx consortium 2017, 'Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution', Nature, vol. 545, no. 7655, pp. 446-451. https://doi.org/10.1038/nature22364

TY - JOUR

T1 - Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

AU - Abbosh, Christopher

AU - Birkbak, Nicolai J

AU - Wilson, Gareth A

AU - Jamal-Hanjani, Mariam

AU - Constantin, Tudor

AU - Salari, Raheleh

AU - Le Quesne, John

AU - Moore, David A

AU - Veeriah, Selvaraju

AU - Rosenthal, Rachel

AU - Marafioti, Teresa

AU - Kirkizlar, Eser

AU - Watkins, Thomas B K

AU - McGranahan, Nicholas

AU - Ward, Sophia

AU - Martinson, Luke

AU - Riley, Joan

AU - Fraioli, Francesco

AU - Al Bakir, Maise

AU - Grönroos, Eva

AU - Zambrana, Francisco

AU - Endozo, Raymondo

AU - Bi, Wenya Linda

AU - Fennessy, Fiona M

AU - Sponer, Nicole

AU - Johnson, Diana

AU - Laycock, Joanne

AU - Shafi, Seema

AU - Czyzewska-Khan, Justyna

AU - Rowan, Andrew

AU - Chambers, Tim

AU - Matthews, Nik

AU - Turajlic, Samra

AU - Hiley, Crispin

AU - Lee, Siow Ming

AU - Forster, Martin D

AU - Ahmad, Tanya

AU - Falzon, Mary

AU - Borg, Elaine

AU - Lawrence, David

AU - Hayward, Martin

AU - Kolvekar, Shyam

AU - Panagiotopoulos, Nikolaos

AU - Janes, Sam M

AU - Thakrar, Ricky

AU - Ahmed, Asia

AU - Blackhall, Fiona

AU - Summers, Yvonne

AU - Hafez, Dina

AU - Middleton, Gary

AU - TRACERx consortium

PY - 2017/5/25

Y1 - 2017/5/25

N2 - 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.

AB - 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.

KW - Non-small-cell lung cancer

KW - Tumour heterogeneity

KW - Metastasis

KW - Diagnostic markers

KW - Predictive markers

U2 - 10.1038/nature22364

DO - 10.1038/nature22364

M3 - Article

C2 - 28445469

SN - 0028-0836

VL - 545

SP - 446

EP - 451

JO - Nature

JF - Nature

IS - 7655

ER -

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Abstract

Keywords

UN SDGs

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