Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA102645 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene array analysis of anaplastic thyroid carcinoma cell lines versus normal thyroid cell lines
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Project description:Gene expression profiling of human anaplastic thyroid carcinoma cells by microarray
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Project description:Gene array analysis of anaplastic thyroid carcinoma tissue versus matched and unmatched normal thyroid tissue
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Project description:A comparison of profiles of normal thryoid tissue (NT), papillary thyroid carcinoma tissue (PTC) and anaplastic thyroid carcinoma tissue (ATC) was carried out to identify expression patterns specifically associated with analplastic thyroid carcinoma Keywords: Expression profile survey of normal tissue and tumor subtypes
2007-09-21 | GSE9115 | GEO
Project description:Anaplastic thyroid carcinoma (ATC) has among the worst prognosis of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. BRAF and TP53 mutations co-occur in a high proportion of ATC, particularly those associated with a precursor papillary thyroid carcinoma (PTC). In order to develop an adult-onset model of BRAF-mutant anaplastic thyroid carcinoma, we generated a novel thyroid-specific CreER transgenic mouse. We utilize a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from papillary to anaplastic thyroid carcinoma. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis and rapid lethality. We employed small animal ultrasound imaging to monitor autochthonous tumors, and show that treatment with the selective BRAF inhibitor PLX4720 improved survival, but did not lead to tumor regression or suppress signaling through the MAPK pathway. Combination of PLX4720 and the MEK inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines, and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. Total RNA from five murine papillary thyroid carcinoma (PTC) tumors and five murine anaplastic thyroid carcinoma (ATC) tumors was analyzed.
2014-04-02 | E-GEOD-55933 | biostudies-arrayexpress
Project description:The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with very high mortality. Double-stranded RNA–directed RNA interference (dsRNAi) targeting the PIAS2 isoform beta (PIAS2b) inhibits growth of ATC cell lines and patient primary cultures in vitro and orthotopic patient-derived xenografts (oPDX) in vivo, but not of thyroid cell lines or non-anaplastic primary thyroid cultures (differentiated carcinoma, benign lesions, or normal). PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. Strikingly, PIAS2b-dsRNAi induces mitotic catastrophe at prophase. High-throughput proteomics revealed the proteasome (PSMC5) and spindle cytoskeleton as direct targets of PIAS2b SUMOylation at mitotic initiation. PIAS2b-dsRNAi is a promising therapy for ATC and other aggressive anaplastic cancers.
2024-04-08 | PXD044110 | Pride
Project description:Anaplastic thyroid carcinoma cell lines (HTH83 and TL3) infected with LAMC2 shRNA
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Project description:Folate modulation induces chromosomal instability and higher proliferation of immortalized human keratinocytes
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Project description:Distant metastasis (DM) is the most important prognostic factor affecting overall survival (OS) of thyroid cancer. The current study aimed to discover prognostic biomarkers to predict thyroid cancer survival, particularly PTC, the most common subtype of thyroid cancer. Four RNA-seq datasets of experimental lung metastasis from 4 transgenic mouse models of PTC, follicular thyroid cancer (FTC), poorly-differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC) were integrated to screen for candidate genes involved in DM. TCGA-THCA dataset were used to validate the candidate genes. A total of 105 up-regulated and 25 down-regulated differentially expressed genes (DEGs) were identified to be present in all 4 datasets. Regulation of cytokine production, inflammation, immune checkpoint regulation, MAPK/ERK cascade were major enriched pathways in metastatic tumor cells. We identified 7 genes whose overexpression was present in 63 of 498 PTC samples (13%) and was associated with poor OS (p<0.01). Clinically, the 7–gene expression signature was associated with older age at the diagnosis, late stage of tumor, tall-cell variant, and higher aneuploidy and hypoxia score. Mutation load was increased in samples with 7–gene expression signature: 26 samples had more than one driver mutations (47%, 26/55). Deep deletions in other chromosomal locus were frequently found in samples with BRAFV600E point mutations. In contrast, only 7% samples without the 7-gene expression signature had more than one driver mutations (24/243). Increased copy number variants (CNVs) were also observed in metastatic as compared to primary tumor cells such as large deletions and duplications. We conclude that the 7–gene expression signature is associated with poor prognosis and chromosomal instability. It may be a useful biomarker for risk stratification for DM and help decision-making in initial surgical recommendations.
2024-12-19 | GSE284225 | GEO