Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA140287 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Clinical and genomic evidence support the view that the metastatic potential of a primary tumor may be dictated by transforming events acquired early in the tumorigenic process. It has been proposed that the presence of such pro-metastatic events in early-stage tumors reflects their additional capability to function as oncogenes. Here, to test this ‘deterministic’ hypothesis and identify potential pro-metastasis oncogenes, we adopted a comparative oncogenomics-guided functional genetic screening strategy involving (i) global transcriptomic data from two genetically engineered mouse models of melanoma with contrasting metastatic potential, (ii) genomic and transcriptomic profiles of human primary and metastatic melanoma and (iii) an invasion screen in TERT-immortalized human melanocytes and melanoma cells in vitro as well as (iv) evidence of expression selection in human melanoma tissues. This integrated effort led to the identification of 6 genes that are both potently pro-invasive and oncogenic. Further, we show that one such pro-invasion oncogene, ACP5, can confer spontaneous metastasis in vivo, engages a key pathway governing metastasis and is prognostic in human primary melanomas.
2011-07-11 | GSE29074 | GEO
Project description:Clinical and genomic evidence support the view that the metastatic potential of a primary tumor may be dictated by transforming events acquired early in the tumorigenic process. It has been proposed that the presence of such pro-metastatic events in early-stage tumors reflects their additional capability to function as oncogenes. Here, to test this ‘deterministic’ hypothesis and identify potential pro-metastasis oncogenes, we adopted a comparative oncogenomics-guided functional genetic screening strategy involving (i) global transcriptomic data from two genetically engineered mouse models of melanoma with contrasting metastatic potential, (ii) genomic and transcriptomic profiles of human primary and metastatic melanoma and (iii) an invasion screen in TERT-immortalized human melanocytes and melanoma cells in vitro as well as (iv) evidence of expression selection in human melanoma tissues. This integrated effort led to the identification of 6 genes that are both potently pro-invasive and oncogenic. Further, we show that one such pro-invasion oncogene, ACP5, can confer spontaneous metastasis in vivo, engages a key pathway governing metastasis and is prognostic in human primary melanomas. The tetracycline-inducible MET-driven mouse (iMet) model (Tyr-rtTA;Tet-Met;Ink4a/Arf-/-) was constructed similar to the previously described iHRAS* model (Tyr-rtTA;Tet-HRASV12G;Ink4a/Arf-/-). RNA from cutaneous melanomas derived from iMet (n=6) or iHRAS* (n=6) models were profiled on Affymetrix M430A_2 chips and resultant transcriptomes were compared to generate a phenotype-based (metastatic capable or not) differentially expressed gene list. Cross-species triangulation to human gene expression and copy number aberrations was based on ortholog mapping.
2011-07-11 | E-GEOD-29074 | biostudies-arrayexpress
Project description:We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis, and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1âs robust effects on melanoma cell invasion, metastasis and tumorigenicity. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveal up-regulation of factors involved in diverse cytokine pathways that include the TGFβ signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion. Transcriptome profiling also informed HOXA1âs ability to potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive precursor cell state concomitant with TGFβ activation. Our analysis of publicly available datasets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors. The HOXA1-induced transcription analysis was conducted using RNAs extracted from WM115 cells transduced with either control or HOXA1, followed by hybridization of labeled cDNA onto Affymetrix GeneChips (Human Genome U133Plus2.0).
2013-01-08 | E-GEOD-37136 | biostudies-arrayexpress
Project description:We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis, and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1 robust effects on melanoma cell invasion, metastasis and tumorigenicity. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveal up-regulation of factors involved in diverse cytokine pathways that include the TGF-beta signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion. Transcriptome profiling also informed HOXA1 ability to potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive precursor cell state concomitant with TGF-beta activation. Our analysis of publicly available datasets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors. The HOXA1-induced transcription analysis was conducted using RNAs extracted from SkMel30 cells transduced with either control or HOXA1, followed by hybridization of labeled cDNA onto Affymetrix GeneChips (Human Genome U133Plus2.0).
2013-01-01 | E-GEOD-40422 | biostudies-arrayexpress
Project description:We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis, and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1‘s robust effects on melanoma cell invasion, metastasis and tumorigenicity. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveal up-regulation of factors involved in diverse cytokine pathways that include the TGFβ signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion. Transcriptome profiling also informed HOXA1’s ability to potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive precursor cell state concomitant with TGFβ activation. Our analysis of publicly available datasets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors.
2013-01-01 | GSE40422 | GEO
Project description:We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis, and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1‘s robust effects on melanoma cell invasion, metastasis and tumorigenicity. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveal up-regulation of factors involved in diverse cytokine pathways that include the TGFβ signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion. Transcriptome profiling also informed HOXA1’s ability to potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive precursor cell state concomitant with TGFβ activation. Our analysis of publicly available datasets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors.
2013-01-08 | GSE37136 | GEO
Project description:PGCs undergo two distinct stages of demethylation before reaching a hypomethylated ground state at E13.5. Stage 1 occurs between E7.25- E9.5 in which PGCs experience a global loss of cytosine methylation. However, discreet loci escape this global loss of methylation and between E10.5-E13.5, stage 2 of demethylation takes place. In this stage these loci are targeted by Tet1 and Tet2 leading to the loss of the remaining methylation and resulting in the epigenetic ground state. Our data shows that Dnmt1 is responsible for maintaining the methylation of loci that escape stage 1 demethylation, and that it functions in a UHRF1 independent manner. Our data further demonstrates that when these loci lose methylation prior to stage 2 it results in early activation of the meiotic program, which leads to precocious differentiation of the germ line resulting in a decreased pool of PGCs in the embryo and subsequent infertility in adult mice.
2016-09-13 | GSE74938 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description: Not available
| S-EPMC11335981 | biostudies-literature
Project description:Tumors frequently found in dogs include canine oral tumors, either cancerous or noncancerous. The bloodstream is an important route for tumor metastasis, particularly for late-stage oral melanoma (LOM) and late-stage oral squamous cell carcinoma (LOSCC). The present study aimed to investigate serum peptidome-based biomarkers of dogs with early-stage oral melanoma, LOM, LOSCC, benign oral tumors, chronic periodontitis and healthy controls, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and liquid chromatography tandem mass spectrometry.
2023-09-28 | PXD037051 | JPOST Repository