Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma

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

doi:10.1038/s41467-021-21068-9

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Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma

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Peer reviewed

Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma

Ziad Bakouny, David A Braun, Sachet A Shukla, Wenting Pan, Xin Gao, Yue Hou, Abdallah Flaifel, Stephen Tang, Alice Bosma-Moody, Meng Xiao He, …

Nature communications, Vol.12(1), pp.808-808

05/02/2021

DOI: https://doi.org/10.1038/s41467-021-21068-9

PMCID: 7865061

PMID: 33547292

Abstract

Antineoplastic Agents, Immunological - therapeutic use

B7-H1 Antigen - antagonists & inhibitors

B7-H1 Antigen - genetics

B7-H1 Antigen - immunology

Carcinoma, Renal Cell - drug therapy

Carcinoma, Renal Cell - genetics

Carcinoma, Renal Cell - immunology

Carcinoma, Renal Cell - mortality

CTLA-4 Antigen - antagonists & inhibitors

CTLA-4 Antigen - genetics

CTLA-4 Antigen - immunology

Cyclin-Dependent Kinase Inhibitor p16 - genetics

Cyclin-Dependent Kinase Inhibitor p16 - immunology

Gene Expression Profiling

Gene Expression Regulation, Neoplastic

High-Throughput Nucleotide Sequencing

Humans

Immune Checkpoint Inhibitors - therapeutic use

Immune Checkpoint Proteins - genetics

Immune Checkpoint Proteins - immunology

Kidney Neoplasms - drug therapy

Kidney Neoplasms - genetics

Kidney Neoplasms - immunology

Kidney Neoplasms - mortality

Mutation

Programmed Cell Death 1 Receptor - antagonists & inhibitors

Programmed Cell Death 1 Receptor - genetics

Programmed Cell Death 1 Receptor - immunology

Proto-Oncogene Proteins c-myc - genetics

Proto-Oncogene Proteins c-myc - immunology

Retrospective Studies

Rhabdoid Tumor - drug therapy

Rhabdoid Tumor - genetics

Rhabdoid Tumor - immunology

Rhabdoid Tumor - mortality

Signal Transduction

Survival Analysis

Transcription, Genetic

Tumor Suppressor Proteins - genetics

Tumor Suppressor Proteins - immunology

Ubiquitin Thiolesterase - genetics

Ubiquitin Thiolesterase - immunology

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.

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Title: Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma
Creators - without role: Ziad Bakouny - Dana-Farber Cancer Institute
David A Braun - Dana-Farber Cancer Institute
Sachet A Shukla - Dana-Farber Cancer Institute
Wenting Pan - Dana-Farber Cancer Institute
Xin Gao - Massachusetts General Hospital
Yue Hou - Dana-Farber Cancer Institute
Abdallah Flaifel - Brigham and Women's Hospital
Stephen Tang - Dana-Farber Cancer Institute
Alice Bosma-Moody - Dana-Farber Cancer Institute
Meng Xiao He - Dana-Farber Cancer Institute
Natalie Vokes - Dana-Farber Cancer Institute
Jackson Nyman - Dana-Farber Cancer Institute
Wanling Xie - Dana-Farber Cancer Institute
Amin H Nassar - Dana-Farber Cancer Institute
Sarah Abou Alaiwi - Dana-Farber Cancer Institute
Ronan Flippot - Dana-Farber Cancer Institute
Gabrielle Bouchard - Dana-Farber Cancer Institute
John A Steinharter - Dana-Farber Cancer Institute
Pier Vitale Nuzzo - Dana-Farber Cancer Institute
Miriam Ficial - Brigham and Women's Hospital
Miriam Sant'Angelo - Brigham and Women's Hospital
Juliet Forman - Dana-Farber Cancer Institute
Jacob E Berchuck - Dana-Farber Cancer Institute
Shaan Dudani - Baker Hughes
Kevin Bi - Dana-Farber Cancer Institute
Jihye Park - Dana-Farber Cancer Institute
Sabrina Camp - Dana-Farber Cancer Institute
Maura Sticco-Ivins - Brigham and Women's Hospital
Laure Hirsch - Dana-Farber Cancer Institute
Sylvan C Baca - Dana-Farber Cancer Institute
Megan Wind-Rotolo - Bristol-Myers Squibb
Petra Ross-Macdonald - Bristol-Myers Squibb
Maxine Sun - Dana-Farber Cancer Institute
Gwo-Shu Mary Lee - Dana-Farber Cancer Institute
Steven L Chang - Dana-Farber Cancer Institute
Xiao X Wei - Dana-Farber Cancer Institute
Bradley A McGregor - Dana-Farber Cancer Institute
Lauren C Harshman - Dana-Farber Cancer Institute
Giannicola Genovese - The University of Texas MD Anderson Cancer Center
Leigh Ellis - Brigham and Women's Hospital
Mark Pomerantz - Dana-Farber Cancer Institute
Michelle S Hirsch - Brigham and Women's Hospital
Matthew L Freedman - Dana-Farber Cancer Institute
Michael B Atkins - Georgetown University Medical Center
Catherine J Wu - Dana-Farber Cancer Institute
Thai H Ho - Mayo Clinic in Arizona
W Marston Linehan - National Cancer Institute
David F McDermott - Beth Israel Deaconess Medical Center
Daniel Y C Heng - Baker Hughes
Srinivas R Viswanathan - Dana-Farber Cancer Institute
Sabina Signoretti - Brigham and Women's Hospital
Eliezer M Van Allen - Dana-Farber Cancer Institute
Toni K Choueiri - Dana-Farber Cancer Institute
Publication Details: Nature communications, Vol.12(1), pp.808-808
Grant note: R50 CA211482 / NCI NIH HHS R01 CA224917 / NCI NIH HHS F31 CA250136 / NCI NIH HHS P50 CA101942 / NCI NIH HHS R01 CA227388 / NCI NIH HHS
Identifiers: 9944926808331
Academic Unit: King Abdullah University of Science & Technology
Language: English
Resource Type: Journal article