Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma
Abstract
Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings build on prior work and shed light on the molecular drivers of aggressivity and responsiveness to ICI of S/R RCC.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 05, 2021
- Source ID
- 10.1038/s41467-021-21068-9
Entities
People
- Abdallah Flaifel
- Alice Bosma-moody
- Amin H Nassar
- Bradley A. Mcgregor
- Catherine J Wu
- Daniel Y. C. Heng
- David A Braun
- David F McDermott
- Eliezer Van Allen
- Gabrielle Bouchard
- Giannicola Genovese
- Gwo-shu Mary Lee
- Jackson Nyman
- Jacob E Berchuck
- Jihye Park
- John A. Steinharter
- Juliet Forman
- Kevin Bi
- Laure Hirsch
- Lauren C Harshman
- Leigh Ellis
- Mark Pomerantz
- Matthew L Freedman
- Maura Sticco-ivins
- Maxine Sun
- Megan Wind-Rotolo
- Meng Xiao He
- Michael B Atkins
- Michelle S Hirsch
- Miriam Ficial
- Miriam Sant’angelo
- Natalie Vokes
- Petra Ross-macdonald
- Pier Vitale Nuzzo
- Ronan Flippot
- Sabina Signoretti
- Sabrina Camp
- Sachet A Shukla
- Sarah Abou Alaiwi
- Shaan Dudani
- Srinivas R Viswanathan
- Stephen Tang
- Steven L. Chang
- Sylvan C. Baca
- Thai Huu Ho
- Toni K Choueiri
- Wanling Xie
- Wenting Pan
- William Linehan
- Xiao X. Wei
- Xin Gao
- Yue Hou
- Ziad Bakouny
Organizations
- Bristol-Myers Squibb
- Congressionally Directed Medical Research Programs
- Fondation ARC pour la recherche sur le cancer
- Kidney Cancer Association
- National Cancer Institute
- United States Department of Health and Human Services