Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

C Abbosh; NJ Birkbak; M Jamal-Hanjani; T Constantin; R Salari; J Le Quesne; DA Moore; S Veeriah; R Rosenthal; T Marafioti; E Kirkizlar; TBK Watkins; N McGranahan; S Ward; L Martinson; J Riley; F Fraioli; M Al Bakir; E Gronroos; F Zambrana; R Endozo; WL Bi; FM Fennessy; N Sponer; D Johnson; J Laycock; S Shafi; J Czyzewska-Khan; A Rowan; T Chambers; N Matthews; S Turajlic; C Hiley; SM Lee; MD Forster; T Ahmad; M Falzon; E Borg; D Lawrence; M Hayward; S Kolvekar; N Panagioyopoulos; SM Janes; R Thakrar; A Ahmed; Fiona Blackhall; Y Summers; D Hafez; A Naik; A Ganguly; S Kareht; R Shah; L Joseph; AM Quinn; Philip Crosbie; B Naidu; Gary Middleton; G Langman; S Trotter; M Nicolson; H Remmen; K Kerr; M Chetty; L Gomersall; DA Fennell; A Nakas; S Rathinam; G Anand; S Khan; P Russell; V Ezhil; B Ismail; M Irvin-Sellers; V Prakash; JF Lester; M Kornaszewska; R Attanoos; H Adams; H Davies; D Oukrif; AU Akarca; JA Hartley; HL Lowe; S Lock; N Iles; H Bell; Y Ngai; G Elgar; Z Szallasi; RF Schwarz; J Herrero; A Stewart; SA Quezada; KS Peggs; P Van Loo; Caroline Dive; CJ Lin; M Rabinowitz; HJWL Aerts; A Hackshaw; JA Shaw; BG Zimmermann; Charles Swanton

doi:10.1038/nature22364

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

C Abbosh, NJ Birkbak, M Jamal-Hanjani, T Constantin, R Salari, J Le Quesne, DA Moore, S Veeriah, R Rosenthal, T Marafioti, E Kirkizlar, TBK Watkins, N McGranahan, S Ward, L Martinson, J Riley, F Fraioli, M Al Bakir, E Gronroos, F ZambranaR Endozo, WL Bi, FM Fennessy, N Sponer, D Johnson, J Laycock, S Shafi, J Czyzewska-Khan, A Rowan, T Chambers, N Matthews, S Turajlic, C Hiley, SM Lee, MD Forster, T Ahmad, M Falzon, E Borg, D Lawrence, M Hayward, S Kolvekar, N Panagioyopoulos, SM Janes, R Thakrar, A Ahmed, Fiona Blackhall, Y Summers, D Hafez, A Naik, A Ganguly, S Kareht, R Shah, L Joseph, AM Quinn, Philip Crosbie, B Naidu, Gary Middleton, G Langman, S Trotter, M Nicolson, H Remmen, K Kerr, M Chetty, L Gomersall, DA Fennell, A Nakas, S Rathinam, G Anand, S Khan, P Russell, V Ezhil, B Ismail, M Irvin-Sellers, V Prakash, JF Lester, M Kornaszewska, R Attanoos, H Adams, H Davies, D Oukrif, AU Akarca, JA Hartley, HL Lowe, S Lock, N Iles, H Bell, Y Ngai, G Elgar, Z Szallasi, RF Schwarz, J Herrero, A Stewart, SA Quezada, KS Peggs, P Van Loo, Caroline Dive, CJ Lin, M Rabinowitz, HJWL Aerts, A Hackshaw, JA Shaw, BG Zimmermann, Charles Swanton

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

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
Journal	Nature
Volume	545
Early online date	26 Apr 2017
DOIs	https://doi.org/10.1038/nature22364
Publication status	Published - 25 May 2017

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Manchester Cancer Research Centre

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10.1038/nature22364

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Abbosh, C., Birkbak, NJ., 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., Gronroos, E., ... Swanton, C. (2017). Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature, 545, 446–451. https://doi.org/10.1038/nature22364

@article{296b942060514e9484f4e0f0611a8785,

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.",

author = "C Abbosh and NJ Birkbak and M Jamal-Hanjani and T Constantin and R Salari and {Le Quesne}, J and DA Moore and S Veeriah and R Rosenthal and T Marafioti and E Kirkizlar and TBK Watkins and N McGranahan and S Ward and L Martinson and J Riley and F Fraioli and {Al Bakir}, M and E Gronroos and F Zambrana and R Endozo and WL Bi and FM Fennessy and N Sponer and D Johnson and J Laycock and S Shafi and J Czyzewska-Khan and A Rowan and T Chambers and N Matthews and S Turajlic and C Hiley and SM Lee and MD Forster and T Ahmad and M Falzon and E Borg and D Lawrence and M Hayward and S Kolvekar and N Panagioyopoulos and SM Janes and R Thakrar and A Ahmed and Fiona Blackhall and Y Summers and D Hafez and A Naik and A Ganguly and S Kareht and R Shah and L Joseph and AM Quinn and Philip Crosbie and B Naidu and Gary Middleton and G Langman and S Trotter and M Nicolson and H Remmen and K Kerr and M Chetty and L Gomersall and DA Fennell and A Nakas and S Rathinam and G Anand and S Khan and P Russell and V Ezhil and B Ismail and M Irvin-Sellers and V Prakash and JF Lester and M Kornaszewska and R Attanoos and H Adams and H Davies and D Oukrif and AU Akarca and JA Hartley and HL Lowe and S Lock and N Iles and H Bell and Y Ngai and G Elgar and Z Szallasi and RF Schwarz and J Herrero and A Stewart and SA Quezada and KS Peggs and {Van Loo}, P and Caroline Dive and CJ Lin and M Rabinowitz and HJWL Aerts and A Hackshaw and JA Shaw and BG Zimmermann and Charles Swanton",

year = "2017",

month = may,

day = "25",

doi = "10.1038/nature22364",

language = "English",

volume = "545",

pages = "446–451",

journal = "Nature",

issn = "0028-0836",

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Abbosh, C, Birkbak, NJ, 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, Gronroos, 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, Panagioyopoulos, N, Janes, SM, Thakrar, R, Ahmed, A, Blackhall, F, Summers, Y, Hafez, D, Naik, A, Ganguly, A, Kareht, S, Shah, R, Joseph, L, Quinn, AM, Crosbie, P, Naidu, B, Middleton, G, Langman, G, Trotter, S, Nicolson, M, Remmen, H, Kerr, K, Chetty, M, Gomersall, L, Fennell, DA, Nakas, A, Rathinam, S, Anand, G, Khan, S, Russell, P, Ezhil, V, Ismail, B, Irvin-Sellers, M, Prakash, V, Lester, JF, Kornaszewska, M, Attanoos, R, Adams, H, Davies, H, Oukrif, D, Akarca, AU, Hartley, JA, Lowe, HL, Lock, S, Iles, N, Bell, H, Ngai, Y, Elgar, G, Szallasi, Z, Schwarz, RF, Herrero, J, Stewart, A, Quezada, SA, Peggs, KS, Van Loo, P, Dive, C, Lin, CJ, Rabinowitz, M, Aerts, HJWL, Hackshaw, A, Shaw, JA, Zimmermann, BG & Swanton, C 2017, 'Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution', Nature, vol. 545, pp. 446–451. https://doi.org/10.1038/nature22364

TY - JOUR

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

AU - Abbosh, C

AU - Birkbak, NJ

AU - Jamal-Hanjani, M

AU - Constantin, T

AU - Salari, R

AU - Le Quesne, J

AU - Moore, DA

AU - Veeriah, S

AU - Rosenthal, R

AU - Marafioti, T

AU - Kirkizlar, E

AU - Watkins, TBK

AU - McGranahan, N

AU - Ward, S

AU - Martinson, L

AU - Riley, J

AU - Fraioli, F

AU - Al Bakir, M

AU - Gronroos, E

AU - Zambrana, F

AU - Endozo, R

AU - Bi, WL

AU - Fennessy, FM

AU - Sponer, N

AU - Johnson, D

AU - Laycock, J

AU - Shafi, S

AU - Czyzewska-Khan, J

AU - Rowan, A

AU - Chambers, T

AU - Matthews, N

AU - Turajlic, S

AU - Hiley, C

AU - Lee, SM

AU - Forster, MD

AU - Ahmad, T

AU - Falzon, M

AU - Borg, E

AU - Lawrence, D

AU - Hayward, M

AU - Kolvekar, S

AU - Panagioyopoulos, N

AU - Janes, SM

AU - Thakrar, R

AU - Ahmed, A

AU - Blackhall, Fiona

AU - Summers, Y

AU - Hafez, D

AU - Naik, A

AU - Ganguly, A

AU - Kareht, S

AU - Shah, R

AU - Joseph, L

AU - Quinn, AM

AU - Crosbie, Philip

AU - Naidu, B

AU - Middleton, Gary

AU - Langman, G

AU - Trotter, S

AU - Nicolson, M

AU - Remmen, H

AU - Kerr, K

AU - Chetty, M

AU - Gomersall, L

AU - Fennell, DA

AU - Nakas, A

AU - Rathinam, S

AU - Anand, G

AU - Khan, S

AU - Russell, P

AU - Ezhil, V

AU - Ismail, B

AU - Irvin-Sellers, M

AU - Prakash, V

AU - Lester, JF

AU - Kornaszewska, M

AU - Attanoos, R

AU - Adams, H

AU - Davies, H

AU - Oukrif, D

AU - Akarca, AU

AU - Hartley, JA

AU - Lowe, HL

AU - Lock, S

AU - Iles, N

AU - Bell, H

AU - Ngai, Y

AU - Elgar, G

AU - Szallasi, Z

AU - Schwarz, RF

AU - Herrero, J

AU - Stewart, A

AU - Quezada, SA

AU - Peggs, KS

AU - Van Loo, P

AU - Dive, Caroline

AU - Lin, CJ

AU - Rabinowitz, M

AU - Aerts, HJWL

AU - Hackshaw, A

AU - Shaw, JA

AU - Zimmermann, BG

AU - Swanton, Charles

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.

UR - https://research.birmingham.ac.uk/portal/en/publications/phylogenetic-ctdna-analysis-depicts-earlystage-lung-cancer-evolution(546fedcd-9d37-4f82-9636-e77e602b3aac).html

U2 - 10.1038/nature22364

DO - 10.1038/nature22364

M3 - Article

SN - 0028-0836

VL - 545

SP - 446

EP - 451

JO - Nature

JF - Nature

ER -

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Abstract

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