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| Status |
Public on Nov 22, 2021 |
| Title |
Integrative Clinical and Molecular Characterization of Translocation Renal Cell Carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 multiple 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 many targeted therapies. Consistently, we find that outcomes for patients with tRCC treated with vascular endothelial growth factor receptor inhibitors (VEGFR-TKI) are worse than those treated with immune checkpoint inhibition (ICI). Multiparametric immunofluorescence confirmed the presence of CD8+ tumor-infiltrating T cells compatible with a clinical benefit from ICI and revealed 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.
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| Overall design |
6 cell line conditions, 3 replicates each, including 2 control conditions. The 4 study conditions are: ASPS-TFE3 PRCC-TFE3 SFPQ-TFE3 NONO-TFE3 The two control conditions are: WT TFE3 Mock
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| Contributor(s) |
Bakouny Z, Van Allen EM, Choueiri TK, Viswanathan SR |
| Citation(s) |
34986355 |
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| Submission date |
Nov 15, 2021 |
| Last update date |
Feb 21, 2022 |
| Contact name |
Ziad Bakouny |
| E-mail(s) |
ziad_elbakouny@dfci.harvard.edu
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| Organization name |
Dana-Farber Cancer Institute
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| Lab |
Viswanathan Lab
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| Street address |
450 Brookline Ave
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (18)
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| GSM5691492 |
293T cells, ASPS-TFE3 transduced replicate 1 |
| GSM5691493 |
293T cells, SFPQ-TFE3 transduced replicate 1 |
| GSM5691494 |
293T cells, PRCC-TFE3 transduced replicate 1 |
| GSM5691495 |
293T cells, NONO-TFE3 transduced replicate 1 |
| GSM5691496 |
293T cells, WT TFE3 transduced replicate 1 |
| GSM5691497 |
293T cells, Mock transduction replicate 1 |
| GSM5691498 |
293T cells, ASPS-TFE3 transduced replicate 2 |
| GSM5691499 |
293T cells, SFPQ-TFE3 transduced replicate 2 |
| GSM5691500 |
293T cells, PRCC-TFE3 transduced replicate 2 |
| GSM5691501 |
293T cells, NONO-TFE3 transduced replicate 2 |
| GSM5691502 |
293T cells, WT TFE3 transduced replicate 2 |
| GSM5691503 |
293T cells, Mock transduction replicate 2 |
| GSM5691504 |
293T cells, ASPS-TFE3 transduced replicate 3 |
| GSM5691505 |
293T cells, SFPQ-TFE3 transduced replicate 3 |
| GSM5691506 |
293T cells, PRCC-TFE3 transduced replicate 3 |
| GSM5691507 |
293T cells, NONO-TFE3 transduced replicate 3 |
| GSM5691508 |
293T cells, WT TFE3 transduced replicate 3 |
| GSM5691509 |
293T cells, Mock transduction replicate 3 |
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| Relations |
| BioProject |
PRJNA780561 |
| SRA |
SRP346224 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE188885_RAW.tar |
45.9 Mb |
(http)(custom) |
TAR (of RESULTS) |
| GSE188885_Supplementary_Table_3a.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE188885_Supplementary_Table_3b.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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