Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA128161 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The purpose of this study was to investigate the presence of a gene expression signature in BRAF V600E melanomas compared to wild type ones, all derived from sun-exposed sites. Microdissected tissues from excisional biopsies of 18 cutaneous melanomas were analyzed to detect the presence of BRAF and NRAS mutations and to profile whole genome expression by means of oligonucleotide microarrays. Class comparison methods were used to select differentially expressed genes between wild type and mutated lesions. Real Time RT-PCR and immunohistochemistry were applied to validate differences at the mRNA and protein levels on an independent cohort of samples. BRAF mutations were evidenced in 67% of melanomas. All of them consisted of the oncogenic change V600E (and the mutation event was independent of Clark's level). Data indicate that in V600E melanomas there is an over-expression of cancer stem cell markers and an upregulation of important oncogenes, like KRAS. This, together with the downregulation of genes involved in oxidative UV stress response and immuno system defense, confers an advantage to V600E melanomas compared to wt lesions. Moreover, the downregulation of topoisomerase I and CDKN2A results in an increased replicative potential associated with a decrease in senescence markers and a diminished DNA damage response. As far as the wild-type lesions, we interestingly pointed out the overexpression of PML, PIK3CA and the downregulation of two tumour suppressor genes (BRCA1 and TP73) relevant to DNA repair.
2024-12-31 | GSE22838 | GEO
Project description:We found that pigmented and amelanotic (MPNST-like) melanomas arise in the genetically engineered BRAF(V600E)-Cdk4(R24C) mouse melanoma model and even in the same animal. To explore the molecular differences between the two type of melanomas in this model we performed global gene expression profiling and pathway analysis to compare the underlying mechanisms. This information was used to identify human melanomas that resemble each type of the mouse melanomas found in the in the genetically engineered BRAF(V600E)-Cdk4(R24C) mouse melanoma model.
2015-12-01 | GSE71879 | GEO
Project description:Among the myriad tumors analyzed to date, cutaneous malignant melanomas bear some of the highest mutational burdens. Thus, it is somewhat surprising that oncogene exclusion between is so pronounced in melanomas where there is only a single melanoma out of 366 sequenced specimens which harbors concurrent BRAF(V600E/M) and NRAS(G13R) mutations (TCGA-ES-A2NC Sample; WWW.bioportal.org), In this senario some NRAS and BRAF mutations co-expressing cells show slow growth phenotypes by under study mechanism. We used Affymetrix GeneChip Expression Arrays to detail the global programme of gene expression underlying oncogenic exclusion and identified distinct classes of up and down-regulated genes during this process.
2018-11-22 | GSE122835 | GEO
Project description:Investigation of expression differences between melanomas harvested from MiniCoopR-GFP versus MiniCoopR-SETDB1 transgenic zebrafish. An eight-chip study using total RNA prepared from four distinct melanomas from zebrafish injected with MiniCoopR-GFP (control) transposon and four distinct melanomas from zebrafish injected with MiniCoopR-SETDB1 transposon. Injected animals carried a p53 loss-of-function mutation, a mutation in nacre, and an mitf:BRAF-V600E transgene. Each chip measures the expression level of 32,292 genes.
2011-01-07 | E-GEOD-21505 | biostudies-arrayexpress
Project description:Chronic sun-damaged (CSDhigh) melanoma represents 10-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events, or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 73 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole-exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1 and TP53 mutations (P < 0.01, Fisher’s Exact Test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with > 95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.
2020-05-19 | GSE139362 | GEO
Project description:We studied the effects of endogenous expression of the melanoma oncogene RAC1 P29S in BRAF V600E;PTEN hemizygous mouse melanomas.
2018-08-10 | GSE118344 | GEO
Project description:Fifty percent of cutaneous melanomas are driven by activated BRAFV600E, but tumors treated with RAF inhibitors, even when they respond dramatically, rapidly adapt and develop resistance. Thus, there is a pressing need to identify the major mechanisms of intrinsic and adaptive resistance and develop drug combinations that target these resistance mechanisms. In a combinatorial drug screen on a panel of 12 treatment-naïve BRAFV600E mutant melanoma cell lines of varying levels of resistance to MAPK pathway inhibition we identified the combination PLX4720, a targeted inhibitor of mutated BRaf, and lapatinib, an inhibitor of the ERBB family of receptor tyrosine kinases, as synergistically cytotoxic in the subset of cell lines that displayed the most resistance to PLX4720. To identify potential mechanisms of resistance to PLX4720 treatment and synergy with lapatinib treatment we performed a multi-platform functional genomics analysis to profile the genome as well as the transcriptional and proteomic responses of these cell lines to treatment with PLX4720. We found modest levels of resistance correlated with the zygosity of the BRAF V600E allele and RTK mutational status. Layered over base-line resistance was substantial upregulation of many ERBB pathway genes in response to BRaf inhibition, thus generating the vulnerability to combination with lapatinib. The transcriptional responses of ERBB pathway genes are associated with a number of transcription factors, including ETS2 and its associated cofactors that represent a convergent regulatory mechanism conferring synergistic drug susceptibility in the context of diverse mutational landscapes. 12 BRAF mutant melanomas and 4 melanomas with WT BRAF were exposed plx4720 treatment to evaluate their responses after 8 hours of treatment. 5 of the 12 BRAF mutant melanomas responses were also evaluated in response to the treatment of lapatinib alone, masitinib alone, the combination of lapatinib with plx4720, or the combination of masitinib with plx4720. All samples were run in at least triplicate.
2015-09-16 | E-GEOD-68453 | biostudies-arrayexpress
Project description:ETV1 is amplified in a subset of melanomas. Here, we performed RNA-seq on two BRAF V600E mutant melonoma cell lines transduced with a scrambed shRNA and two individual ETV1 shRNA
2018-04-15 | GSE80352 | GEO
Project description:BRAF interactomes dependent on the mutation V600E are analyzed by SEC-PCP-SILAC and HA-IPs comparing V600E to WT
2017-01-03 | PXD004585 | Pride
Project description:Low grade neuroepithelial tumor is the major cause of epilepsy Low-grade neuroepithelial tumors are major causes of drug-resistant focal epilepsy. The BRAF V600E mutation is frequently observed in low grade neuroepithelial tumor and linked to poor seizure outcomes. However, its molecular role in epileptogenicity remains elusive. To understand the molecular mechanism underlying the epileptogenicity in LEAT with the BRAF V600E genetic mutation (BRAF V600E-LEAT), we conducted RNA sequencing (RNA-seq) analysis using surgical specimens of BRAF V600E-LEAT obtained and stored at a single institute. bioinformatics analysis using this dataset identified 2,134 differentially expressed genes between BRAF V600E-LEAT and control. Additionally, gene set enrichment analysis provided novel insights into the association between estrogen response-related pathways and the epileptogenicity of BRAF V600E-LEAT patients.
2024-01-02 | GSE252323 | GEO