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 languageEnglish
    Article numbere1001906
    JournalP L o S Biology
    Volume12
    Issue number7
    Number of pages7
    ISSN1544-9173
    DOIs
    Publication statusPublished - 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

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