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Renal medullary carcinoma (RMC) is a rare and deadly kidney cancer in patients of African descent with sickle cell trait. We have developed faithful patient-derived RMC models and using whole-genome sequencing, we identified loss-of-function intronic fusion events in one SMARCB1 allele with concurrent loss of the other allele. Biochemical and functional characterization of these models revealed that RMC requires the loss of SMARCB1 for survival. Through integration of RNAi and CRISPR-Cas9 loss-of-function genetic screens and a small-molecule screen, we found that the ubiquitin-proteasome system (UPS) was essential in RMC. Inhibition of the UPS caused a G2/M arrest due to constitutive accumulation of cyclin B1. These observations extend across cancers that harbor SMARCB1 loss, which also require expression of the E2 ubiquitin-conjugating enzyme, UBE2C. Our studies identify a synthetic lethal relationship between SMARCB1-deficient cancers and reliance on the UPS which provides the foundation for a mechanism-informed clinical trial with proteasome inhibitors.
Pubmed ID: 30860482 RIS Download
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Software that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries.
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View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsA software package to analyze next-generation resequencing data. The toolkit offers a wide variety of tools, with a primary focus on variant discovery and genotyping as well as strong emphasis on data quality assurance. Its robust architecture, powerful processing engine and high-performance computing features make it capable of taking on projects of any size. This software library makes writing efficient analysis tools using next-generation sequencing data very easy, and second it's a suite of tools for working with human medical resequencing projects such as 1000 Genomes and The Cancer Genome Atlas. These tools include things like a depth of coverage analyzers, a quality score recalibrator, a SNP/indel caller and a local realigner. (entry from Genetic Analysis Software)
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsAdjusting batch effects in microarray expression data using Empirical Bayes methods.
View all literature mentionsThis monoclonal targets UBE2C
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View all literature mentionsThis polyclonal targets CCND1, CCND2
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis recombinant monoclonal targets GAPDH
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View all literature mentionsThis monoclonal targets KALRN
View all literature mentionsThis monoclonal targets Casp3
View all literature mentionsThis polyclonal targets c-Myc
View all literature mentionsThis unknown targets Cyclin B1
View all literature mentionsThis polyclonal targets MYC
View all literature mentionsThis unknown targets BAF57/SMARCE1
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View all literature mentionsThis monoclonal targets SMARCD1
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis monoclonal targets Mouse BAF47 aa. 257-359
View all literature mentionsThis monoclonal targets ARID1A
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line RPMI-8226 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line G-401 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H2172 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line JMSU-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name CrTac:NCr-Foxn1nu from IMSR.
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