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; Bishoy M. Faltas

doi:10.1038/s41467-019-10873-y

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. RubinSeth P. Lerner, Surena F. Matin, Olivier Elemento, Bishoy M. Faltas

Urology

Research output: Contribution to journal › Article › peer-review

129 Scopus citations

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.

Original language	English (US)
Article number	2977
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10873-y
State	Published - Dec 1 2019

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Robinson, B. D., Vlachostergios, P. J., Bhinder, B., Liu, W., Li, K., Moss, T. J., Bareja, R., Park, K., Tavassoli, P., Cyrta, J., Tagawa, S. T., Nanus, D. M., Beltran, H., Molina, A. M., Khani, F., Miguel Mosquera, J., Xylinas, E., Shariat, S. F., Scherr, D. S., ... Faltas, B. M. (2019). Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling. Nature communications, 10(1), Article 2977. https://doi.org/10.1038/s41467-019-10873-y

Robinson, BD, Vlachostergios, PJ, Bhinder, B, Liu, W, Li, K, Moss, TJ, Bareja, R, Park, K, Tavassoli, P, Cyrta, J, Tagawa, ST, Nanus, DM, Beltran, H, Molina, AM, Khani, F, Miguel Mosquera, J, Xylinas, E, Shariat, SF, Scherr, DS, Rubin, MA, Lerner, SP, Matin, SF, Elemento, O & Faltas, BM 2019, 'Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling', Nature communications, vol. 10, no. 1, 2977. https://doi.org/10.1038/s41467-019-10873-y

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

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.",

author = "Robinson, {Brian D.} and Vlachostergios, {Panagiotis J.} and Bhavneet Bhinder and Weisi Liu and Kailyn Li and Moss, {Tyler J.} and Rohan Bareja and Kyung Park and Peyman Tavassoli and Joanna Cyrta and Tagawa, {Scott T.} and Nanus, {David M.} and Himisha Beltran and Molina, {Ana M.} and Francesca Khani and {Miguel Mosquera}, Juan and Evanguelos Xylinas and Shariat, {Shahrokh F.} and Scherr, {Douglas S.} and Rubin, {Mark A.} and Lerner, {Seth P.} and Matin, {Surena F.} and Olivier Elemento and Faltas, {Bishoy M.}",

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T1 - Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling

AU - Robinson, Brian D.

AU - Vlachostergios, Panagiotis J.

AU - Bhinder, Bhavneet

AU - Liu, Weisi

AU - Li, Kailyn

AU - Moss, Tyler J.

AU - Bareja, Rohan

AU - Park, Kyung

AU - Tavassoli, Peyman

AU - Cyrta, Joanna

AU - Tagawa, Scott T.

AU - Nanus, David M.

AU - Beltran, Himisha

AU - Molina, Ana M.

AU - Khani, Francesca

AU - Miguel Mosquera, Juan

AU - Xylinas, Evanguelos

AU - Shariat, Shahrokh F.

AU - Scherr, Douglas S.

AU - Rubin, Mark A.

AU - Lerner, Seth P.

AU - Matin, Surena F.

AU - Elemento, Olivier

AU - Faltas, Bishoy M.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

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