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GSE85898
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Three of the melanoma cell lines show higher expression fold change after stimulation than the other 3.
Publication Title
Loss of IFN-γ Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
Ion Torrent Proton
Description
We sought to characterize expression profiles signifying the development of atypical adenomatous hyperplasia (AAH) from normal lung parenchyma (NL), and its progression to lung adenocarcinomas (LUAD). Overall design: We performed transcriptome sequencing of 48 samples, comprising NLs, AAHs and LUADs, from 17 patients. Sequencing was performed using the Ion Torrent platform afterwhich gene profiles differentially expressed among the three groups were determined.
Publication Title
Genomic Landscape of Atypical Adenomatous Hyperplasia Reveals Divergent Modes to Lung Adenocarcinoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18INK4C and p16INK4A codeletion. Functional reconstitution of p18INK4C in GBM cells null for both p16INK4A and p18INK4C resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16INK4A-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16INK4A in primary astrocytes induced a concomitant increase in p18INK4C. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation.
Publication Title
Feedback circuit among INK4 tumor suppressors constrains human glioblastoma development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18INK4C and p16INK4A codeletion. Functional reconstitution of p18INK4C in GBM cells null for both p16INK4A and p18INK4C resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16INK4A-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16INK4A in primary astrocytes induced a concomitant increase in p18INK4C. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation.
Publication Title
Feedback circuit among INK4 tumor suppressors constrains human glioblastoma development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
SMARCA2 and SMARCA4 are two mutually exclusive ATPase subunits of SWI/SNF complex. SMARCA4 deficient lung cancer population selectively depend on SMARCA2 for cancer growth phenotype. Rescue experiments with ectopic expression of wild-type, bromodomain mutant and ATPase dead SMARCA2 and SMARCA4 highlight that ATPase domain is the drug target.
Publication Title
The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We have sampled several tumour regions from nine clear cell renal cell carcinoma (ccRCC) patients to investigate intra-tumour heterogeneity.
Publication Title
Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Clariom S Human array (clariomshuman)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Clariom S Human array (clariomshuman)
Description
Lung cancer is a devastating disease that remains the top cause of cancer mortality. While targeted therapies against EGFR and EML4-ALK fusion and recent advances in immunotherapy have shown substantial clinical benefit for some patients, the vast majority of patients with lung cancer still lack effective therapies underscoring the dire need for more context-specific therapeutics. Cancer genomic studies have identified frequent genetic alterations in chromatin and epigenetic regulators including inactivating mutations in components of the SWI/SNF chromatin remodeling complex. In lung adenocarcinoma, about 20% of tumors have inactivating mutations in components of the SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A. With the aim of understanding the mechanism of tumor development driven by mutations in this complex, we developed a genetically engineered mouse (GEM) model of lung adenocarcinoma by selectively ablating Smarca4 in the lung epithelium. We demonstrate that Smarca4 acts as a bona fide tumor suppressor and cooperates with p53 loss and Kras activation. Cross species integrative gene expression analyses revealed signature of enhanced oxidative phosphorylation (OXPHOS) in SMARCA4 mutant murine as well as human lung adenocarcinomas. We further show that SMARCA4 mutant cells have increased oxygen consumption and increased respiratory capacity primarily driven by increased expression of the mitochondrial master regulator, PGC1-. Importantly, we show that SMARCA4 and other SWI/SNF mutant lung cancer cell lines and xenograft tumors have exquisite sensitivity to inhibition of OXPHOS by a novel small molecule, IACS-010759, that is under clinical development. Mechanistically, we show that SMARCA4 deficient cells have a blunted transcriptional response to energy stress creating a therapeutically attractive collateral vulnerability. These findings provide the mechanistic basis for further development of OXPHOS inhibitors as therapeutics against SWI/SNF mutant tumors.
Publication Title
Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 82 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PBRM1 was found to be mutated in a high percentage of clear cell RCCs. We performed knockdown of PBRM1 via siRNA and compared with scrambled control in three different RCC cell lines.
Publication Title
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 99 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Oral Cavity Cancer
Publication Title
A 13-gene signature prognostic of HPV-negative OSCC: discovery and external validation.
Sample Metadata Fields
Sex
View Samples