Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling

Brian D. Robinson, Panagiotis J. Vlachostergios, Bhavneet Bhinder, Weisi Liu, Kailyn Li, Tyler J. Moss, Rohan Bareja, Kyung Park, Peyman Tavassoli, Joanna Cyrta, Scott T. Tagawa, David M. Nanus, Himisha Beltran, Ana M. Molina, Francesca Khani, Juan Miguel Mosquera, Evanguelos Xylinas, Shahrokh F. Shariat, Douglas S. Scherr, Mark A. Rubin, Seth P. Lerner, Surena F. Matin, Olivier Elemento and Bishoy M. Faltas ()
Additional contact information
Brian D. Robinson: Weill Cornell Medicine
Panagiotis J. Vlachostergios: Weill Cornell Medicine
Bhavneet Bhinder: Weill Cornell Medicine
Weisi Liu: Weill Cornell Medicine
Kailyn Li: Weill Cornell Medicine
Tyler J. Moss: The University of Texas MD Anderson Cancer Center
Rohan Bareja: Weill Cornell Medicine
Kyung Park: Weill Cornell Medicine
Peyman Tavassoli: Weill Cornell Medicine
Joanna Cyrta: Weill Cornell Medicine
Scott T. Tagawa: Weill Cornell Medicine
David M. Nanus: Weill Cornell Medicine
Himisha Beltran: Weill Cornell Medicine
Ana M. Molina: Weill Cornell Medicine
Francesca Khani: Weill Cornell Medicine
Juan Miguel Mosquera: Weill Cornell Medicine
Evanguelos Xylinas: Weill Cornell Medicine
Shahrokh F. Shariat: Weill Cornell Medicine
Douglas S. Scherr: Weill Cornell Medicine
Mark A. Rubin: Weill Cornell Medicine
Seth P. Lerner: Baylor College of Medicine
Surena F. Matin: The University of Texas MD Anderson Cancer Center
Olivier Elemento: Weill Cornell Medicine
Bishoy M. Faltas: Weill Cornell Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10873-y

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