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.
Nature communications. 2024 Mar 18*** epublish ***
Kentaro Ohara, André Figueiredo Rendeiro, Bhavneet Bhinder, Kenneth Wha Eng, Hiranmayi Ravichandran, Duy Nguyen, David Pisapia, Aram Vosoughi, Evan Fernandez, Kyrillus S Shohdy, Jyothi Manohar, Shaham Beg, David Wilkes, Brian D Robinson, Francesca Khani, Rohan Bareja, Scott T Tagawa, Madhu M Ouseph, Andrea Sboner, Olivier Elemento, Bishoy M Faltas, Juan Miguel Mosquera
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., Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, 10065, USA., Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA. ., Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA. .