Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma.
IF: 17.694
Cited by: 63


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.


Spatial Transcriptomics

MeSH terms

Antineoplastic Agents, Immunological
B7-H1 Antigen
CTLA-4 Antigen
Carcinoma, Renal Cell
Cyclin-Dependent Kinase Inhibitor p16
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
High-Throughput Nucleotide Sequencing
Immune Checkpoint Inhibitors
Immune Checkpoint Proteins
Kidney Neoplasms
Programmed Cell Death 1 Receptor
Proto-Oncogene Proteins c-myc
Retrospective Studies
Rhabdoid Tumor
Signal Transduction
Survival Analysis
Transcription, Genetic
Tumor Suppressor Proteins
Ubiquitin Thiolesterase


Bakouny, Ziad
Braun, David A
Shukla, Sachet A
Pan, Wenting
Gao, Xin
Hou, Yue
Flaifel, Abdallah
Tang, Stephen
Bosma-Moody, Alice
He, Meng Xiao
Vokes, Natalie
Nyman, Jackson
Xie, Wanling
Nassar, Amin H
Abou Alaiwi, Sarah
Flippot, Ronan
Bouchard, Gabrielle
Steinharter, John A
Nuzzo, Pier Vitale
Ficial, Miriam
Sant'Angelo, Miriam
Forman, Juliet
Berchuck, Jacob E
Dudani, Shaan
Bi, Kevin
Park, Jihye
Camp, Sabrina
Sticco-Ivins, Maura
Hirsch, Laure
Baca, Sylvan C
Wind-Rotolo, Megan
Ross-Macdonald, Petra
Sun, Maxine
Lee, Gwo-Shu Mary
Chang, Steven L
Wei, Xiao X
McGregor, Bradley A
Harshman, Lauren C
Genovese, Giannicola
Ellis, Leigh
Pomerantz, Mark
Hirsch, Michelle S
Freedman, Matthew L
Atkins, Michael B
Wu, Catherine J
Ho, Thai H
Linehan, W Marston
McDermott, David F
Heng, Daniel Y C
Viswanathan, Srinivas R
Signoretti, Sabina
Van Allen, Eliezer M
Choueiri, Toni K

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