Genomic mapping of metastatic organotropism in lung adenocarcinoma.

View 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.

Investigators
Abbreviation
Cancer Cell
Publication Date
2023-04-08
Pubmed ID
37084736
Medium
Print-Electronic
Full Title
Genomic mapping of metastatic organotropism in lung adenocarcinoma.
Authors
Lengel HB, Mastrogiacomo B, Connolly JG, Tan KS, Liu Y, Fick CN, Dunne EG, He D, Lankadasari MB, Satravada BA, Sun Y, Kundra R, Fong C, Smith S, Riely GJ, Rudin CM, Gomez DR, Solit DB, Berger MF, Li BT, Mayo MW, Matei I, Lyden DC, Adusumilli PS, Schultz N, Sanchez-Vega F, Jones DR