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The evolution of non-small cell lung cancer metastases in TRACERx

Authors :
Al Bakir, Maise
Huebner, Ariana
Martínez-Ruiz, Carlos
Grigoriadis, Kristiana
Watkins, Thomas B. K.
Pich, Oriol
Moore, David A.
Veeriah, Selvaraju
Ward, Sophia
Laycock, Joanne
Johnson, Diana
Rowan, Andrew
Razaq, Maryam
Akther, Mita
Naceur-Lombardelli, Cristina
Prymas, Paulina
Toncheva, Antonia
Hessey, Sonya
Dietzen, Michelle
Colliver, Emma
Frankell, Alexander M.
Bunkum, Abigail
Lim, Emilia L.
Karasaki, Takahiro
Abbosh, Christopher
Hiley, Crispin T.
Hill, Mark S.
Cook, Daniel E.
Wilson, Gareth A.
Salgado, Roberto
Nye, Emma
Stone, Richard Kevin
Fennell, Dean A.
Price, Gillian
Kerr, Keith M.
Naidu, Babu
Middleton, Gary
Summers, Yvonne
Lindsay, Colin R.
Blackhall, Fiona H.
Cave, Judith
Blyth, Kevin G.
Nair, Arjun
Ahmed, Asia
Taylor, Magali N.
Procter, Alexander James
Falzon, Mary
Lawrence, David
Navani, Neal
Thakrar, Ricky M.
Janes, Sam M.
Papadatos-Pastos, Dionysis
Forster, Martin D.
Lee, Siow Ming
Ahmad, Tanya
Quezada, Sergio A.
Peggs, Karl S.
Van Loo, Peter
Dive, Caroline
Hackshaw, Allan
Birkbak, Nicolai J.
Zaccaria, Simone
Jamal-Hanjani, Mariam
McGranahan, Nicholas
Swanton, Charles
Source :
Nature; April 2023, Vol. 616 Issue: 7957 p534-542, 9p
Publication Year :
2023

Abstract

Metastatic 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.

Details

Language :
English
ISSN :
00280836 and 14764687
Volume :
616
Issue :
7957
Database :
Supplemental Index
Journal :
Nature
Publication Type :
Periodical
Accession number :
ejs62797225
Full Text :
https://doi.org/10.1038/s41586-023-05729-x