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dc.contributor.authorFennell, Dean
dc.date.accessioned2023-08-01T11:27:55Z
dc.date.available2023-08-01T11:27:55Z
dc.date.issued2023-04-12
dc.identifier.citationAl Bakir, M., Huebner, A., Martínez-Ruiz, C., Grigoriadis, K., Watkins, T. B. K., Pich, O., Moore, D. A., Veeriah, S., Ward, S., Laycock, J., Johnson, D., Rowan, A., Razaq, M., Akther, M., Naceur-Lombardelli, C., Prymas, P., Toncheva, A., Hessey, S., Dietzen, M., Colliver, E., … Swanton, C. (2023). The evolution of non-small cell lung cancer metastases in TRACERx. Nature, 616(7957), 534–542. https://doi.org/10.1038/s41586-023-05729-xen_US
dc.identifier.other10.1038/s41586-023-05729-x
dc.identifier.urihttp://hdl.handle.net/20.500.12904/17421
dc.description.abstractMetastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.
dc.description.urihttps://www.nature.com/articles/s41586-023-05729-xen_US
dc.language.isoenen_US
dc.titleThe evolution of non-small cell lung cancer metastases in TRACERxen_US
dc.typeArticleen_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US
rioxxterms.versionNAen_US
rioxxterms.versionofrecordhttps://doi.org/10.1038/s41586-023-05729-xen_US
rioxxterms.typeJournal Article/Reviewen_US
refterms.panelUnspecifieden_US
html.description.abstractMetastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.en_US
rioxxterms.funder.project94a427429a5bcfef7dd04c33360d80cden_US


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