Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

Mariam Jamal-Hanjani; Alan Hackshaw; Yenting Ngai; Jacqueline Shaw; Caroline Dive; Sergio Quezada; Gary Middleton; Elza de Bruin; John Le Quesne; Seema Shafi; Mary Falzon; Stuart Horswell; Fiona Blackhall; Iftekhar Khan; Sam Janes; Marianne Nicolson; David Lawrence; Martin Forster; Dean Fennell; Siow-Ming Lee; Jason Lester; Keith Kerr; Salli Muller; Natasha Iles; Sean Smith; Nirupa Murugaesu; Richard Mitter; Max Salm; Aengus Stuart; Nik Matthews; Haydn Adams; Tanya Ahmad; Richard Attanoos; Jonathan Bennett; Nicolai Juul Birkbak; Richard Booton; Ged Brady; Keith Buchan; Arrigo Capitano; Mahendran Chetty; Mark Cobbold; Philip Crosbie; Helen Davies; Alan Denison; Madhav Djearman; Jacki Goldman; Tom Haswell; Leena Joseph; Malgorzata Kornaszewska; Matthew Krebs; Gerald Langman; Mairead MacKenzie; Joy Millar; Bruno Morgan; Babu Naidu; Daisuke Nonaka; Karl Peggs; Catrin Pritchard; Hardy Remmen; Andrew Rowan; Rajesh Shah; Elaine Smith; Yvonne Summers; Magali Taylor; Selvaraju Veeriah; David Waller; Ben Wilcox; Maggie Wilcox; Ian Woolhouse; Nicholas McGranahan; Charles Swanton

doi:10.1371/journal.pbio.1001906

Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

Mariam Jamal-Hanjani, Alan Hackshaw, Yenting Ngai, Jacqueline Shaw, Caroline Dive, Sergio Quezada, Gary Middleton, Elza de Bruin, John Le Quesne, Seema Shafi, Mary Falzon, Stuart Horswell, Fiona Blackhall, Iftekhar Khan, Sam Janes, Marianne Nicolson, David Lawrence, Martin Forster, Dean Fennell, Siow-Ming LeeJason Lester, Keith Kerr, Salli Muller, Natasha Iles, Sean Smith, Nirupa Murugaesu, Richard Mitter, Max Salm, Aengus Stuart, Nik Matthews, Haydn Adams, Tanya Ahmad, Richard Attanoos, Jonathan Bennett, Nicolai Juul Birkbak, Richard Booton, Ged Brady, Keith Buchan, Arrigo Capitano, Mahendran Chetty, Mark Cobbold, Philip Crosbie, Helen Davies, Alan Denison, Madhav Djearman, Jacki Goldman, Tom Haswell, Leena Joseph, Malgorzata Kornaszewska, Matthew Krebs, Gerald Langman, Mairead MacKenzie, Joy Millar, Bruno Morgan, Babu Naidu, Daisuke Nonaka, Karl Peggs, Catrin Pritchard, Hardy Remmen, Andrew Rowan, Rajesh Shah, Elaine Smith, Yvonne Summers, Magali Taylor, Selvaraju Veeriah, David Waller, Ben Wilcox, Maggie Wilcox, Ian Woolhouse, Nicholas McGranahan, Charles Swanton

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Abstract

The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.

Original language	English
Article number	e1001906
Journal	P L o S Biology
Volume	12
Issue number	7
Number of pages	7
ISSN	1544-9173
DOIs	https://doi.org/10.1371/journal.pbio.1001906
Publication status	Published - 2014

Bibliographical note

Copyright: 2014 Jamal-Hanjani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

clonal heterogeneity
functional heterogeneity
genomic study
intratumour genetic heterogeneity
Lung TRACERx Study
somatic mutational heterogeneity
primary non-small cell lung cancer Carcinoma, Non-Small-Cell Lung (MeSH) Lung Neoplasms (MeSH) respiratory system disease, neoplastic disease
Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common
genes
03502, Genetics - General
03508, Genetics - Human
10062, Biochemistry studies - Nucleic acids, purines and pyrimidines
16006, Respiratory system - Pathology
24004, Neoplasms - Pathology, clinical aspects and systemic effects
Biochemistry and Molecular Biophysics
Human Medicine, Medical Sciences
genetic analysis laboratory techniques, genetic techniques
Molecular Genetics
Oncology
Pulmonary Medicine
BIOCHEMISTRY
BIOLOGY
CHROMOSOMAL INSTABILITY
INTRATUMOR HETEROGENEITY
PROGNOSTIC-SIGNIFICANCE
MUTATIONAL EVOLUTION
ACQUIRED-RESISTANCE
PANCREATIC-CANCER
SOMATIC MUTATIONS
CLONAL SELECTION
BREAST CANCERS
ADENOCARCINOMA

UN SDGs

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

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Jamal-Hanjani, M., Hackshaw, A., Ngai, Y., Shaw, J., Dive, C., Quezada, S., Middleton, G., de Bruin, E., Le Quesne, J., Shafi, S., Falzon, M., Horswell, S., Blackhall, F., Khan, I., Janes, S., Nicolson, M., Lawrence, D., Forster, M., Fennell, D., ... Swanton, C. (2014). Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study. P L o S Biology, 12(7), Article e1001906. https://doi.org/10.1371/journal.pbio.1001906

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abstract = "The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.",

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author = "Mariam Jamal-Hanjani and Alan Hackshaw and Yenting Ngai and Jacqueline Shaw and Caroline Dive and Sergio Quezada and Gary Middleton and {de Bruin}, Elza and {Le Quesne}, John and Seema Shafi and Mary Falzon and Stuart Horswell and Fiona Blackhall and Iftekhar Khan and Sam Janes and Marianne Nicolson and David Lawrence and Martin Forster and Dean Fennell and Siow-Ming Lee and Jason Lester and Keith Kerr and Salli Muller and Natasha Iles and Sean Smith and Nirupa Murugaesu and Richard Mitter and Max Salm and Aengus Stuart and Nik Matthews and Haydn Adams and Tanya Ahmad and Richard Attanoos and Jonathan Bennett and Birkbak, {Nicolai Juul} and Richard Booton and Ged Brady and Keith Buchan and Arrigo Capitano and Mahendran Chetty and Mark Cobbold and Philip Crosbie and Helen Davies and Alan Denison and Madhav Djearman and Jacki Goldman and Tom Haswell and Leena Joseph and Malgorzata Kornaszewska and Matthew Krebs and Gerald Langman and Mairead MacKenzie and Joy Millar and Bruno Morgan and Babu Naidu and Daisuke Nonaka and Karl Peggs and Catrin Pritchard and Hardy Remmen and Andrew Rowan and Rajesh Shah and Elaine Smith and Yvonne Summers and Magali Taylor and Selvaraju Veeriah and David Waller and Ben Wilcox and Maggie Wilcox and Ian Woolhouse and Nicholas McGranahan and Charles Swanton",

note = "Copyright: 2014 Jamal-Hanjani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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doi = "10.1371/journal.pbio.1001906",

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Jamal-Hanjani, M, Hackshaw, A, Ngai, Y, Shaw, J, Dive, C, Quezada, S, Middleton, G, de Bruin, E, Le Quesne, J, Shafi, S, Falzon, M, Horswell, S, Blackhall, F, Khan, I, Janes, S, Nicolson, M, Lawrence, D, Forster, M, Fennell, D, Lee, S-M, Lester, J, Kerr, K, Muller, S, Iles, N, Smith, S, Murugaesu, N, Mitter, R, Salm, M, Stuart, A, Matthews, N, Adams, H, Ahmad, T, Attanoos, R, Bennett, J, Birkbak, NJ, Booton, R, Brady, G, Buchan, K, Capitano, A, Chetty, M, Cobbold, M, Crosbie, P, Davies, H, Denison, A, Djearman, M, Goldman, J, Haswell, T, Joseph, L, Kornaszewska, M, Krebs, M, Langman, G, MacKenzie, M, Millar, J, Morgan, B, Naidu, B, Nonaka, D, Peggs, K, Pritchard, C, Remmen, H, Rowan, A, Shah, R, Smith, E, Summers, Y, Taylor, M, Veeriah, S, Waller, D, Wilcox, B, Wilcox, M, Woolhouse, I, McGranahan, N & Swanton, C 2014, 'Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study', P L o S Biology, vol. 12, no. 7, e1001906. https://doi.org/10.1371/journal.pbio.1001906

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T1 - Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

AU - Jamal-Hanjani, Mariam

AU - Hackshaw, Alan

AU - Ngai, Yenting

AU - Shaw, Jacqueline

AU - Dive, Caroline

AU - Quezada, Sergio

AU - Middleton, Gary

AU - de Bruin, Elza

AU - Le Quesne, John

AU - Shafi, Seema

AU - Falzon, Mary

AU - Horswell, Stuart

AU - Blackhall, Fiona

AU - Khan, Iftekhar

AU - Janes, Sam

AU - Nicolson, Marianne

AU - Lawrence, David

AU - Forster, Martin

AU - Fennell, Dean

AU - Lee, Siow-Ming

AU - Lester, Jason

AU - Kerr, Keith

AU - Muller, Salli

AU - Iles, Natasha

AU - Smith, Sean

AU - Murugaesu, Nirupa

AU - Mitter, Richard

AU - Salm, Max

AU - Stuart, Aengus

AU - Matthews, Nik

AU - Adams, Haydn

AU - Ahmad, Tanya

AU - Attanoos, Richard

AU - Bennett, Jonathan

AU - Birkbak, Nicolai Juul

AU - Booton, Richard

AU - Brady, Ged

AU - Buchan, Keith

AU - Capitano, Arrigo

AU - Chetty, Mahendran

AU - Cobbold, Mark

AU - Crosbie, Philip

AU - Davies, Helen

AU - Denison, Alan

AU - Djearman, Madhav

AU - Goldman, Jacki

AU - Haswell, Tom

AU - Joseph, Leena

AU - Kornaszewska, Malgorzata

AU - Krebs, Matthew

AU - Langman, Gerald

AU - MacKenzie, Mairead

AU - Millar, Joy

AU - Morgan, Bruno

AU - Naidu, Babu

AU - Nonaka, Daisuke

AU - Peggs, Karl

AU - Pritchard, Catrin

AU - Remmen, Hardy

AU - Rowan, Andrew

AU - Shah, Rajesh

AU - Smith, Elaine

AU - Summers, Yvonne

AU - Taylor, Magali

AU - Veeriah, Selvaraju

AU - Waller, David

AU - Wilcox, Ben

AU - Wilcox, Maggie

AU - Woolhouse, Ian

AU - McGranahan, Nicholas

AU - Swanton, Charles

N1 - Copyright: 2014 Jamal-Hanjani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2014

Y1 - 2014

N2 - The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.

AB - The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.

KW - clonal heterogeneity

KW - functional heterogeneity

KW - genomic study

KW - intratumour genetic heterogeneity

KW - Lung TRACERx Study

KW - somatic mutational heterogeneity

KW - primary non-small cell lung cancer Carcinoma, Non-Small-Cell Lung (MeSH) Lung Neoplasms (MeSH) respiratory system disease, neoplastic disease

KW - Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common

KW - genes

KW - 03502, Genetics - General

KW - 03508, Genetics - Human

KW - 10062, Biochemistry studies - Nucleic acids, purines and pyrimidines

KW - 16006, Respiratory system - Pathology

KW - 24004, Neoplasms - Pathology, clinical aspects and systemic effects

KW - Biochemistry and Molecular Biophysics

KW - Human Medicine, Medical Sciences

KW - genetic analysis laboratory techniques, genetic techniques

KW - Molecular Genetics

KW - Oncology

KW - Pulmonary Medicine

KW - BIOCHEMISTRY

KW - BIOLOGY

KW - CHROMOSOMAL INSTABILITY

KW - INTRATUMOR HETEROGENEITY

KW - PROGNOSTIC-SIGNIFICANCE

KW - MUTATIONAL EVOLUTION

KW - ACQUIRED-RESISTANCE

KW - PANCREATIC-CANCER

KW - SOMATIC MUTATIONS

KW - CLONAL SELECTION

KW - BREAST CANCERS

KW - ADENOCARCINOMA

U2 - 10.1371/journal.pbio.1001906

DO - 10.1371/journal.pbio.1001906

M3 - Journal article

C2 - 25003521

SN - 1544-9173

VL - 12

JO - P L o S Biology

JF - P L o S Biology

IS - 7

M1 - e1001906

ER -

Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

Abstract

Bibliographical note

Keywords

UN SDGs

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