Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA96123 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Recent cancer genome sequencing studies have identified numerous novel candidate driver genes. In vivo functional investigation of oncogenes using somatic gene transfer has been successfully exploited as a versatile means to validate their pathogenic relevance. In contrast, such functional analyses have been hampered for candidate tumor suppressor genes, e.g. by insufficient knockdown using RNAi-mediated approaches. In order to provide a flexible method for investigating loss-of-function mutations and their potential role in tumorigenesis, we have established CRISPR/Cas9-mediated somatic gene disruption, allowing for in vivo deletion of candidate tumor suppressor genes. We demonstrate the utility of this approach by somatic disruption of the Ptch1 gene in the mouse cerebellum, leading to the formation of medulloblastoma faithfully resembling the SHH-driven subgroup of the disease. This in vivo method for validation of candidate tumor suppressor genes provides a fast and convenient system for the generation of faithful animal models of human cancer.
2014-12-31 | GSE58629 | GEO
Project description:Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer
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Project description:Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer
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Project description:Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer
| PRJNA270339 | ENA
Project description:Inhibition of the nonsense mediated decay (NMD) mechanism in cells results in stabilization of transcripts carrying premature translation termination codons. A strategy referred to as gene indentification by NMD inhibition (GINI) has been proposed to identify genes carrying nonsense mutations (Noensie & Dietz, 2001). Genes containing frameshift mutations in colon cancer cell line have been identifying mutatnt genes using GINI, we have now further improved the strategy. In this approach, inhibition of NMD with emetine is complemented with inhibiting NMD by blocking the phosphorylation of the hUpf1 protein with caffeine. In addition, to enhance the GINI strategy, comparing mRNA level alterations produced by inhibiting transcription alone or inhbiiting transcription together with NMD following caffeine pretreatment were used for the efficient identification of false positives produced as a result of stress response to NMD inhibition. To demonstrate the improved efficiency of this approach, we analyzed colon cancer cell lines showing microstellite instability. Bi-allelic inactivating mutations were found in the FXR1, SEC1L1, NCOR1, BAT3, PHD14, ZNF294, C190ORF5 genes as well as genes coding for proteins with yet unknown functions. Keywords: microarray, gene expression, Affymetrix, drug treatment, emetine, caffeine, actinomycin D, novel tumor suppressor gene candidates
2006-08-11 | GSE5486 | GEO
Project description:CIC encodes a transcriptional repressor inactivated by loss-of-function mutations in several cancer types, indicating that it may function as a tumor suppressor. Recent data indicate that CIC may regulate cell cycle genes in humans; however, a thorough investigation of this proposed role has not yet been reported. Here, we used single-cell RNA sequencing technology to provide evidence that inactivation of CIC in human cell lines resulted in transcriptional dysregulation of genes involved in cell cycle control. We also mapped CIC’s protein-protein and genetic interaction networks, identifying interactions between CIC and members of the Switch/Sucrose Non-Fermenting (SWI/SNF) complex, as well as novel candidate interactions between CIC and cell cycle regulators. We further showed that CIC loss was associated with an increased frequency of mitotic defects in human cell lines and a mouse model. Overall, our study positions CIC as a cell cycle regulator and indicates that CIC loss can lead to mitotic errors, consistent with CIC’s emerging role as a tumor suppressor of relevance in several cancer contexts.
2023-06-30 | PXD030942 | Pride
Project description:In this study, we identify leucyl-tRNA synthetase (LARS) as a breast tumor suppressor. To identify the mechanism underlying LARS-mediated breast tumor suppression, we conducted TMT-proteomics in PyMT mouse tumors with monoallelic genetic deletion of LARS in the mammary tumor compartment. The analyses implicate LARS as a regulator of leucine-rich protein translation resulting in downregulation of candidate leucine-rich tumor suppressor genes.
2022-01-10 | PXD026609 | Pride
Project description:Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in 30–40% of human colorectal cancers (CRC). However, specific therapeutics against KRAS-mutated CRC have not been established. We have previously reported mouse models for colon cancer with and without Kras mutations (CDX2P-G22Cre;Apcflox/flox; KrasG12D and CDX2P-G22Cre;Apcflox/flox mice, respectively). Herein, we aimed to identify candidate genes as novel therapeutic targets or biomarkers for KRAS-mutated CRC by comparing the gene expression profiles of these two mouse models.
2015-12-25 | GSE75435 | GEO
Project description:A screen to identify novel tumor suppressor genes silenced by methylation in melanoma
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