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| Item Type: | Article |
|---|---|
| Title: | The evolution of non-small cell lung cancer metastases in TRACERx |
| Creators Name: | Al 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., Frankell, A.M., Bunkum, A., Lim, E.L., Karasaki, T., Abbosh, C., Hiley, C.T., Hill, M.S., Cook, D.E., Wilson, G.A., Salgado, R., Nye, E., Stone, R.K., Fennell, D.A., Price, G., Kerr, K.M., Naidu, B., Middleton, G., Summers, Y., Lindsay, C.R., Blackhall, F.H., Cave, J., Blyth, K.G., Nair, A., Ahmed, A., Taylor, M.N., Procter, A.J., Falzon, M., Lawrence, D., Navani, N., Thakrar, R.M., Janes, S.M., Papadatos-Pastos, D., Forster, M.D., Lee, S.M., Ahmad, T., Quezada, S.A., Peggs, K.S., Van Loo, P., Dive, C., Hackshaw, A., Birkbak, N.J., Zaccaria, S., Jamal-Hanjani, M., 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. |
| Keywords: | Clonal Evolution, Clone Cells, Cohort Studies, Disease Progression, Local Neoplasm Recurrence, Lung Neoplasms, Molecular Evolution, Neoplasm Metastasis, Non-Small-Cell Lung Carcinoma |
| Source: | Nature |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Volume: | 616 |
| Number: | 7957 |
| Page Range: | 534-542 |
| Date: | April 2023 |
| Additional Information: | Tom L. Kaufmann is a member of the TRACERx Consortium. |
| Official Publication: | https://doi.org/10.1038/s41586-023-05729-x |
| PubMed: | View item in PubMed |
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