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

Robinson, Brian D; Vlachostergios, Panagiotis J; Bhinder, Bhavneet; Liu, Weisi; Li, Kailyn; Moss, Tyler J; Bareja, Rohan; Park, Kyung; Tavassoli, Peyman; Cyrta, Joanna; Tagawa, Scott T; Nanus, David M; Beltran, Himisha; Molina, Ana M; Khani, Francesca; Miguel Mosquera, Juan; Xylinas, Evanguelos; Shariat, Shahrokh F; Scherr, Douglas S; Rubin, Mark A.; ... (2019). Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling. Nature Communications, 10(1), p. 2977. Springer Nature 10.1038/s41467-019-10873-y

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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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