Genomic mapping of metastatic organotropism in lung adenocarcinoma.

Autor:	Lengel HB; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Mastrogiacomo B; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Connolly JG; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Tan KS; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Liu Y; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Fick CN; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Dunne EG; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., He D; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Lankadasari MB; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Satravada BA; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Sun Y; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Kundra R; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Fong C; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Smith S; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Riely GJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Rudin CM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Gomez DR; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Solit DB; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Berger MF; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Li BT; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Mayo MW; Department of Biochemistry & Molecular Genetics, University of Virginia, Charlottesville, VA, USA., Matei I; Department of Pediatrics, Meyer Cancer Center, Weill Cornell Medicine of Cornell University, New York, NY, USA., Lyden DC; Department of Pediatrics, Meyer Cancer Center, Weill Cornell Medicine of Cornell University, New York, NY, USA., Adusumilli PS; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Schultz N; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Sanchez-Vega F; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: sanchezf@mskcc.org., Jones DR; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: jonesd2@mskcc.org.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2023 May 08; Vol. 41 (5), pp. 970-985.e3. Date of Electronic Publication: 2023 Apr 20.
DOI:	10.1016/j.ccell.2023.03.018
Abstrakt:	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. Competing Interests: Declaration of interests C.M.R. has consulted regarding oncology drug development with AbbVie, Amgen, Astra Zeneca, Epizyme, Genentech/Roche, Ipsen, Jazz, Lilly, and Syros and serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics. G.J.R. has institutional research funding from Mirait, Takeda, Merck, Roche, Novartis, and Pfizer. D.B.S. has consulted for and received honoraria from Pfizer, Lilly/Loxo Oncology, Vividion Therapeutics, Scorpion Therapeutics, and BridgeBio. M.F.B. has consulted for Eli Lilly and PetDx and has received research funding from Grail, not related to the work presented. D.R.J. is a member of the Advisory Council for Astra Zeneca and a member of the Clinical Trial Steering Committee for Merck. All other authors have no relevant competing interests to disclose. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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