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| Item Type: | Article |
|---|---|
| Title: | The evolution of non-small cell lung cancer metastases in TRACERx |
| Creators Name: | Al Bakir, M. and Huebner, A. and Martínez-Ruiz, C. and Grigoriadis, K. and Watkins, T.B.K. and Pich, O. and Moore, D.A. and Veeriah, S. and Ward, S. and Laycock, J. and Johnson, D. and Rowan, A. and Razaq, M. and Akther, M. and Naceur-Lombardelli, C. and Prymas, P. and Toncheva, A. and Hessey, S. and Dietzen, M. and Colliver, E. and Frankell, A.M. and Bunkum, A. and Lim, E.L. and Karasaki, T. and Abbosh, C. and Hiley, C.T. and Hill, M.S. and Cook, D.E. and Wilson, G.A. and Salgado, R. and Nye, E. and Stone, R.K. and Fennell, D.A. and Price, G. and Kerr, K.M. and Naidu, B. and Middleton, G. and Summers, Y. and Lindsay, C.R. and Blackhall, F.H. and Cave, J. and Blyth, K.G. and Nair, A. and Ahmed, A. and Taylor, M.N. and Procter, A.J. and Falzon, M. and Lawrence, D. and Navani, N. and Thakrar, R.M. and Janes, S.M. and Papadatos-Pastos, D. and Forster, M.D. and Lee, S.M. and Ahmad, T. and Quezada, S.A. and Peggs, K.S. and Van Loo, P. and Dive, C. and Hackshaw, A. and Birkbak, N.J. and Zaccaria, S. and Jamal-Hanjani, M. and McGranahan, N. and Swanton, C. |
| Abstract: | Metastatic disease is responsible for the majority of cancer-related deaths. 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. |
| Source: | Nature |
| ISSN: | 1476-4687 |
| Volume: | 616 |
| Number: | 7957 |
| Page Range: | 534-542 |
| Date: | April 2023 |
| Official Publication: | https://doi.org/10.1038/s41586-023-05729-x |
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