Abstract

Upper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis of whole-exome and RNA sequencing of UTUC. Here we report several key insights from our molecular dissection of this disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has a T-cell depleted immune contexture; 3) High FGFR3 expression is enriched in UTUC and correlates with its T-cell depleted immune microenvironment; 4) Sporadic UTUC is characterized by a lower total mutational burden than urothelial carcinoma of the bladder. Our findings lay the foundation for a deeper understanding of UTUC biology and provide a rationale for the development of UTUC-specific treatment strategies.

Details

Title
Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling
Author
Robinson, Brian D 1 ; Vlachostergios, Panagiotis J 2 ; Bhinder, Bhavneet 3 ; Liu, Weisi 2 ; Li, Kailyn 2 ; Moss, Tyler J 4 ; Bareja, Rohan 3 ; Park, Kyung 5 ; Tavassoli, Peyman 5 ; Cyrta, Joanna 6 ; Tagawa, Scott T 7   VIAFID ORCID Logo  ; Nanus, David M 7 ; Beltran, Himisha 7 ; Molina, Ana M 7 ; Khani, Francesca 1 ; Juan Miguel Mosquera 1 ; Xylinas, Evanguelos 8 ; Shariat, Shahrokh F 9 ; Scherr, Douglas S 10 ; Rubin, Mark A 11   VIAFID ORCID Logo  ; Lerner, Seth P 12 ; Matin, Surena F 13 ; Elemento, Olivier 14 ; Faltas, Bishoy M 15   VIAFID ORCID Logo 

1  Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Urology, Weill Cornell Medicine, New York, NY, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA 
2  Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA 
3  Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA 
4  Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
5  Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA 
6  Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA 
7  Department of Urology, Weill Cornell Medicine, New York, NY, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA; Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, USA 
8  Department of Urology, Weill Cornell Medicine, New York, NY, USA; Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France 
9  Department of Urology, Weill Cornell Medicine, New York, NY, USA; Department of Urology, Medical University of Vienna, Vienna, Austria 
10  Department of Urology, Weill Cornell Medicine, New York, NY, USA 
11  Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Urology, Weill Cornell Medicine, New York, NY, USA; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA; Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, USA; Department of Biomedical Research, University of Bern, Bern, Switzerland 
12  Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA 
13  Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
14  Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, USA 
15  Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA; Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, USA; Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, USA 
Pages
1-11
Publication year
2019
Publication date
Jul 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-10873-y
ProQuest document ID
2252669238
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.