Genomic mapping of metastatic organotropism in lung adenocarcinoma Journal Article
| Authors: | Lengel, H. B.; Mastrogiacomo, B.; Connolly, J. G.; Tan, K. S.; Liu, Y.; Fick, C. N.; Dunne, E. G.; He, D.; Lankadasari, M. B.; Satravada, B. A.; Sun, Y.; Kundra, R.; Fong, C.; Smith, S.; Riely, G. J.; Rudin, C. M.; Gomez, D. R.; Solit, D. B.; Berger, M. F.; Li, B. T.; Mayo, M. W.; Matei, I.; Lyden, D. C.; Adusumilli, P. S.; Schultz, N.; Sanchez-Vega, F.; Jones, D. R. |
| Article Title: | Genomic mapping of metastatic organotropism in lung adenocarcinoma |
| Abstract: | We analyzed 2,532 lung adenocarcinomas (LUAD) to identify the clinicopathological and genomic features associated with metastasis, metastatic burden, organotropism, and metastasis-free survival. Patients who develop metastasis are younger and male, with primary tumors enriched in micropapillary or solid histological subtypes and with a higher mutational burden, chromosomal instability, and fraction of genome doublings. Inactivation of TP53, SMARCA4, and CDKN2A are correlated with a site-specific shorter time to metastasis. The APOBEC mutational signature is more prevalent among metastases, particularly liver lesions. Analyses of matched specimens show that oncogenic and actionable alterations are frequently shared between primary tumors and metastases, whereas copy number alterations of unknown significance are more often private to metastases. Only 4% of metastases harbor therapeutically actionable alterations undetected in their matched primaries. Key clinicopathological and genomic alterations in our cohort were externally validated. In summary, our analysis highlights the complexity of clinicopathological features and tumor genomics in LUAD organotropism. © 2023 Elsevier Inc. |
| Keywords: | genetics; mutation; nuclear protein; lung neoplasms; transcription factor; pathology; transcription factors; nuclear proteins; lung tumor; lung adenocarcinoma; genomics; dna helicases; dna helicase; dna copy number variations; copy number variation; adenocarcinoma of lung; humans; human; male; smarca4 protein, human |
| Journal Title: | Cancer Cell |
| Volume: | 41 |
| Issue: | 5 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2023-05-08 |
| Start Page: | 970 |
| End Page: | 985.e3 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2023.03.018 |
| PUBMED: | 37084736 |
| PROVIDER: | scopus |
| PMCID: | PMC10391526 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding authors are MSK authors: Francisco Sanchez-Vega and David R. Jones -- Source: Scopus |
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