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

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.


Brian D. Robinson,1 Panagiotis J. Vlachostergios,2 Bhavneet Bhinder,3 Weisi Liu,2 Kailyn Li,2 Tyler J. Moss,4  Rohan Bareja,3 Kyung Park,5 Peyman Tavassoli,5 Joanna Cyrta,6 Scott T. Tagawa,7 David M. Nanus, 7 Himisha Beltran,7  Ana M. Molina,7 Francesca Khani,8 Juan Miguel Mosquera,8 Evanguelos Xylinas,9 Shahrokh F. Shariat,10 Douglas S. Scherr,11 Mark A. Rubin,12 Seth P. Lerner,13 Surena F. Matin,14 Olivier Elemento, 15 & Bishoy M. Faltas16

1. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA, Department of Urology, Weill Cornell Medicine, New York, NY, 10065, USA, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA,  2. Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, 10065, USA 3. Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 10065, USA, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA 4. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA 5. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA 6. 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 7.  Department of Urology, 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, Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, 10065, USA 8. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA, Department of Urology, Weill Cornell Medicine, New York, NY, 10065, USA, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA 9. Department of Urology, Weill Cornell Medicine, New York, NY, 10065, USA, Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, 75014, France 10. Department of Urology, Weill Cornell Medicine, New York, NY, 10065, USA, Department of Urology, Medical University of Vienna, Vienna, 1190, Austria 11. Department of Urology, Weill Cornell Medicine, New York, NY, 10065, USA 12. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA, Department of Urology, Weill Cornell Medicine, New York, NY, 10065, USA, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA, Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, 10065, USA, Department of Biomedical Research, University of Bern, Bern, 3008, Switzerland 13. Scott Department of Urology, Baylor College of Medicine, Houston, TX, 77030, USA 14. Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA 15. Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, 10021, USA, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 10065, USA, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA, Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, 10065, USA 16. 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, Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, NY, 10065, USA, Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, 10065, USA


Robinson, Brian D., 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. "Upper Tract Urothelial Carcinoma Has a Luminal-papillary T-cell Depleted Contexture and Activated FGFR3 Signaling." Nature Communications10, no. 1 (July 05, 2019). doi:10.1038/s41467-019-10873-y.