Integrative clinical and molecular characterization of translocation renal cell carcinoma

Ziad Bakouny, Ananthan Sadagopan, Praful Ravi, Nebiyou Y. Metaferia, Jiao Li, Shatha AbuHammad, Stephen Tang, Thomas Denize, Emma R. Garner, Xin Gao, David A. Braun, Laure Hirsch, John A. Steinharter, Gabrielle Bouchard, Emily Walton, Destiny West, Chris Labaki, Shaan Dudani, Chun Loo Gan, Vidyalakshmi SethunathFilipe L.F. Carvalho, Alma Imamovic, Cora Ricker, Natalie I. Vokes, Jackson Nyman, Jacob E. Berchuck, Jihye Park, Michelle S. Hirsch, Rizwan Haq, Gwo Shu Mary Lee, Bradley A. McGregor, Steven L. Chang, Adam S. Feldman, Catherine J. Wu, David F. McDermott, Daniel Y.C. Heng, Sabina Signoretti, Eliezer M. Van Allen, Toni K. Choueiri, Srinivas R. Viswanathan

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Translocation renal cell carcinoma (tRCC) is a poorly characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks of tRCC through an integrative analysis of 152 patients with tRCC identified across genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from MiT/TFE fusions and homozygous deletions at chromosome 9p21.3 (19.2% of cases). Transcriptionally, tRCCs display a heightened NRF2-driven antioxidant response that is associated with resistance to targeted therapies. Consistently, we find that outcomes for patients with tRCC treated with vascular endothelial growth factor receptor inhibitors (VEGFR-TKIs) are worse than those treated with immune checkpoint inhibitors (ICI). Using multiparametric immunofluorescence, we find that the tumors are infiltrated with CD8+ T cells, though the T cells harbor an exhaustion immunophenotype distinct from that of clear cell RCC. Our findings comprehensively define the clinical and molecular features of tRCC and may inspire new therapeutic hypotheses.
Original languageEnglish (US)
JournalCell reports
Volume38
Issue number1
DOIs
StatePublished - Jan 4 2022
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-09-21

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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