Genomic mapping of metastatic organotropism in lung adenocarcinoma.

TitleGenomic mapping of metastatic organotropism in lung adenocarcinoma.
Publication TypeJournal Article
Year of Publication2023
AuthorsLengel HB, Mastrogiacomo B, Connolly JG, Tan KSee, Liu Y, Fick CN, Dunne EG, He D, Lankadasari MB, Satravada BAnusha, 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
JournalCancer Cell
Date Published2023 May 08
KeywordsAdenocarcinoma of Lung, DNA Copy Number Variations, DNA Helicases, Genomics, Humans, Lung Neoplasms, Male, Mutation, Nuclear Proteins, Transcription Factors

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.

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Alternate JournalCancer Cell
PubMed ID37084736
PubMed Central IDPMC10391526
Grant ListT32 CA009501 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
R01 CA236615 / CA / NCI NIH HHS / United States
R01 CA240472 / CA / NCI NIH HHS / United States
R01 CA192399 / CA / NCI NIH HHS / United States
R01 CA217169 / CA / NCI NIH HHS / United States

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