Journal Article

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

Robinson, Brian D., Mosquera, Juan Miguel, Ravichandran, Hiranmayi, Fernandez, Evan, Bhinder, Bhavneet, Shohdy, Kyrillus S., Bareja, Rohan, Ohara, Kentaro, Wilkes, David, Rendeiro, André Figueiredo, Sboner, Andrea, Elemento, Olivier, Tagawa, Scott T., Nguyen, Duy, Vosoughi, Aram, Beg, Shaham, Khani, Francesca, Manohar, Jyothi, Faltas, Bishoy M., Eng, Kenneth Wha, Pisapia, David, Ouseph, Madhu M.

2024

Overview

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. Detailed molecular studies are required to understand the differences between primary and metastatic upper tract urothelial carcinoma (UTUC). Here, the authors use genomics, transcriptomics and imaging mass cytometry to characterise the molecular profiles of primary and metastatic UTUC, and find that molecular subtypes remain highly conserved.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14/1 / 45/23 / 45/91 / 631/67/2329 / 631/67/322 / 631/67/589/1336 / 631/67/69 / Antibodies / Cancer / Carcinoma, Transitional Cell - genetics / Carcinoma, Transitional Cell - pathology / Cytometry / Evolution / Gene Expression Profiling / Gene sequencing / Genomics / Genomics - methods / Humanities and Social Sciences / Humans / Medical imaging / Metastases / Metastasis / multidisciplinary / Proteins / Science / Science (multidisciplinary) / Single-cell protein / Stromal cells / Transcriptome / Transcriptomics / Tumors / Urinary Bladder Neoplasms - genetics / Urinary Bladder Neoplasms - pathology / Urological cancer / Urothelial carcinoma