The evolution of metastatic upper tract urothelial carcinoma through genomic-transcriptomic and single-cell protein markers analysis.

Autor: Ohara K; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA., Rendeiro AF; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY, 10021, USA.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT 25.3, 1090, Vienna, Austria., Bhinder B; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY, 10021, USA., Eng KW; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY, 10021, USA., Ravichandran H; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA., Nguyen D; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, 10065, USA., Pisapia D; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA., Vosoughi A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA., Fernandez E; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY, 10021, USA., Shohdy KS; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, 10065, USA., Manohar J; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA., Beg S; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA., Wilkes D; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA., Robinson BD; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA., Khani F; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA., Bareja R; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY, 10021, USA., Tagawa ST; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, 10065, USA.; Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, 10065, USA., Ouseph MM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA., Sboner A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY, 10021, USA., Elemento O; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, 1305 York Avenue, New York, NY, 10021, USA.; Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, 10065, USA., Faltas BM; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA. bmf9003@med.cornell.edu.; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, 10065, USA. bmf9003@med.cornell.edu.; Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, 10065, USA. bmf9003@med.cornell.edu.; Departments of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, 10065, USA. bmf9003@med.cornell.edu., Mosquera JM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA. jmm9018@med.cornell.edu.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA. jmm9018@med.cornell.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Mar 18; Vol. 15 (1), pp. 2009. Date of Electronic Publication: 2024 Mar 18.
DOI: 10.1038/s41467-024-46320-w
Abstrakt: The molecular characteristics of metastatic upper tract urothelial carcinoma (UTUC) are not well understood, and there is a lack of knowledge regarding the genomic and transcriptomic differences between primary and metastatic UTUC. To address these gaps, we integrate whole-exome sequencing, RNA sequencing, and Imaging Mass Cytometry using lanthanide metal-conjugated antibodies of 44 tumor samples from 28 patients with high-grade primary and metastatic UTUC. We perform a spatially-resolved single-cell analysis of cancer, immune, and stromal cells to understand the evolution of primary to metastatic UTUC. We discover that actionable genomic alterations are frequently discordant between primary and metastatic UTUC tumors in the same patient. In contrast, molecular subtype membership and immune depletion signature are stable across primary and matched metastatic UTUC. Molecular and immune subtypes are consistent between bulk RNA-sequencing and mass cytometry of protein markers from 340,798 single cells. Molecular subtypes at the single-cell level are highly conserved between primary and metastatic UTUC tumors within the same patient.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: