Lyve1+ cells expressing BRAFV600E show hepatic vascular cavernomas in developing murine liver.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE147848 | GEO | 2020/05/06
REPOSITORIES: GEO
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Project description:Lyve1+ cells expressing BRAFV600E show hepatic vascular cavernomas in developing murine liver.
| PRJNA622278 | ENA
Project description:BRAFV600E mutation is the most frequent molecular event in papillary thyroid carcinoma. The relation of this genetic alteration with the factors od poor prognosis has been reported as well as its influence on PTC gene signature. However human material disables distinction of cancer causes from its effect. We used our transgenic mouse model of papillary thyroid carcinoma induced by the BRAFV600E mutation to select BRAFV600E-specific gene signature The transgenic mouse model was obtained by the microinjection of the transgene, composed of the human BRAF cDNA with V600E mutation under the control of bovine thyroglobulin, into the ferilized mice egg cells. Three lines were derived and mice after 4-24 months were sacrificed and histopathological evaluation of thyroids was carried out. In order to find BRAFV600E-specific gene signature microarray analysis was performed. The analysis invloved 38 mice thyroid samples: 10 mice papillary thyroid carcinomas, 10 borderline lesions (all being BRAF-positive), 10 apparently asymptomatic thyroids (5 BRAF-positive and 5 BRAF-negative) and 8 benign hyperplastic lesions (4 BRAF-positive and 4 BRAF-negative). Multofactoral analyses were performed in order to define some additional factors that could have impact on the gene expression profile.
2015-12-31 | E-GEOD-58546 | biostudies-arrayexpress
Project description:Vemurafenib is a BRAF inhibitor with specificity for the most common BRAF mutant encountered in melanomas (BRAFV600E). Vemurafenib suppresses the proliferation of BRAF mutant human melanoma cells by suppressing downstream activation of the MEK/ERK mitogen activated protein kinases. We used microarrays to examine the transcriptional response of a vemurafenib-sensitive BRAFV600E human melanoma cell line (A375) to vemurafenib in order to further delineate the mechanisms by which BRAFV600E drives cell proliferation and energy metabolism in human melanoma. BRAFV600E A375 human melanoma cells were treated with vehicle (0.1% DMSO) or 10 uM vemurafenib for 24 h after which total RNA was extracted. Cells were prepared and RNA was extracted in 3 separate batches (three different cell stocks on three separate days) providing three independent replicates (n=3). Paired replicates (prepared from the same stock of cells on the same day) are denoted by A, B and C.
2014-05-20 | E-GEOD-42872 | biostudies-arrayexpress
Project description:Vemurafenib is a BRAF inhibitor with specificity for the most common BRAF mutant encountered in melanomas (BRAFV600E). Vemurafenib suppresses the proliferation of BRAF mutant human melanoma cells by suppressing downstream activation of the MEK/ERK mitogen activated protein kinases. We used microarrays to examine the transcriptional response of a vemurafenib-sensitive BRAFV600E human melanoma cell line (A375) to vemurafenib in order to further delineate the mechanisms by which BRAFV600E drives cell proliferation and energy metabolism in human melanoma.
2014-05-20 | GSE42872 | GEO
Project description:Transcriptional profiling of mouse NIH3T3 cells comparing control NIH3T3 cells transfected with a pEFm6-BRAF with cells transfected with pEFm6-BRAFV600E. Goal was to determine the effects of BRAFV600E gene transfection on global mouse NIH3T3 cells gene expression.
2017-01-01 | GSE90589 | GEO
Project description:Most cancer genomics papers to date have focused on aberrations in genomic DNA and protein-coding transcripts. However, around 50% of transcripts have no coding potential and may exist as non-coding RNA. We performed RNA-seq in BRAFv600e melanoma skin cancer and on melanocytes over-expressing oncogenic BRAF to catalog transcriptome remodeling. We discovered that BRAF regulates expression of 1027 protein coding transcripts, 39 annotated lncRNAs and 70 novel transcripts. Many of the novel transcripts are lncRNAs. We used an indepenedent dataset to interrogate our novel transcripts and found that the novel lncRNA BANCR is a BRAF-regulated lncRNA recurrently upregulated in melanoma. Knockdown of BANCR impairs melanoma cell migration. Whole transcriptome RNA-seq followed assembly to Refseq/Gencode and de novo transcript assembly. RNA-seq performed on: 2 BRAFv600e melanomas, melanocytes+RFP control and melanocytes + BRAFv600e. We discovered protein-coding transcripts, annotated ncRNAs and novel transcripts (including lncRNAs) regulated by BRAFv600e also coordinately expressed in melanoma.
2012-04-28 | E-GEOD-33092 | biostudies-arrayexpress
Project description:In spite of the advancements in targeted therapy for BRAFV600E-mutated metastatic colorectal cancer (mCRC), the development of resistance to BRAFV600E inhibition limits the response rate and durability of the treatment. Better understanding of the resistance mechanisms to BRAF inhibitors will facilitate the design of novel pharmacological strategies for BRAF-mutated mCRC. The aim of this study was to identify novel protein candidates involved in acquired resistance to BRAFV600E inhibitor vemurafenib in BRAFV600E-mutated colon cancer cells using an integrated proteomics approach. Our study suggests a role of ezrin in acquired resistance to vemurafenib in colon cancer and melanoma cells carrying BRAFV600E mutation and supports further pre-clinical and clinical studies to explore the benefits of combined BRAF inhibitors and actin-targeting drugs as a potential therapeutic approach for BRAFV600E-mutated cancers.
2023-08-29 | PXD042499 | Pride
Project description:BRAF-inhibitor (BRAFi)-resistance compromises long term survivorship of malignant melanoma patients, and mutant NRAS is a major mediator of BRAFi-resistance. We have employed NanoString nCounterTM transcriptomic analysis of isogenic human malignant melanoma cells that differ only by NRAS mutational status (BRAFi-sensitive A375-BRAFV600E/NRASQ61 versus BRAFi-resistant A375-BRAFV600E/NRASQ61K), identifying modulation of specific gene expression networks as a function of NRASQ61K-status.
2021-09-23 | GSE184633 | GEO
Project description:The oncogenic mutation BRAFV600E is a common event in nevi and melanomas, which are aggressive skin tumors characterized by MAPK signaling pathway activation. It has been observed that mutated benign melanocytic lesions can remain unchanged for decades, but also proliferate or undergo oncogene-induced senescence. The purpose of this study was to investigate the presence of a gene expression signature in BRAFV600E mutated nevi compared to wild-type ones, all derived from sun exposed sites. Microdissected tissues from excisional biopsies of acquired nevi were analyzed to detect the presence of BRAF and NRAS mutations and to profile whole genome expression by means of oligonucleotide microarrays. BRAFV600E mutation was evidenced in 64% of nevi, while no NRAS mutations were detected. Functional analysis of genes differentially expressed between wild-type and mutated lesions pointed out the role of oxidative stress in causing the oncogenic BRAF mutation and that the direct consequence of constitutive activation of BRAF-MEK-ERK pathway, in a benign contest, is the activation of apoptosis, autophagy and senescence. Our data also indicate that in mutated lesions, p53 plays a crucial role in the maintenance of the benign status. In our study, in order to understand the role of BRAF mutation in acquired nevi, we performed gene expression profiling analysis on fourteen lesions derived from intermittently exposed sites, using whole genome oligonucleotide microarrays. Expression data were coupled with sequencing results on BRAF and NRAS genes and class comparison algorithms were applied to detect sequences differentially expressed between BRAFV600E and BRAFwt-NRASwt lesions. Some of the obtained results were further validated by Real-Time RT-PCR on an independent cohort of samples. Mutation analysis evidenced BRAF mutations in 64% of the common acquired nevi. All the mutations consisted in the substitution V600E (T1799A). No alteration was found on exon 11 of the BRAF gene nor on exons 1 and 2 of the NRAS gene, as expected since no lesion came from chronically exposed sites. Transcriptome analysis was carried out using oligo-microarrays and differential expression was tested applying the Linear Models package LIMMA available at www.bioconductor.org that uses Bayesian statistics to compute the probability of a gene being differentially expressed. Only 25 transcripts had B value greater then 2. We then performed a one-way ANOVA, dividing samples into three classes according to their BRAF mutational status (wt, ++, +++) as assessed by pyrosequencing. We found 2882 known transcripts by selecting those with ANOVA p-value<0.01 and increasing or decreasing expression trends along the three classes. Functional analysis was performed using the MetaCoreTM software package to identify overrepresented functional processes. BRAF signature, acquired nevi, gene expression profiling "++ and +++" refer to the percentage of alleles carrying the mutation in the *BRAF*V600E lesions. This has been assessed by pyrosequencing analysis (Venesio et al, 2008. PMID= 18408659).
2016-06-30 | E-GEOD-23976 | biostudies-arrayexpress
Project description:BRAFV600E mutation is the most frequent molecular event in papillary thyroid carcinoma. The relation of this genetic alteration with the factors od poor prognosis has been reported as well as its influence on PTC gene signature. However human material disables distinction of cancer causes from its effect. We used our transgenic mouse model of papillary thyroid carcinoma induced by the BRAFV600E mutation to select BRAFV600E-specifi gene signature which was than compared to human material The human microarray data were obtained for: 27 papillary thyroid carcinomas including 18 BRAF(+), 8 RET(+), 1 RAS(+); 18 apparently healthy thyroids. In order to find BRAFV600E-specific gene signature data obtained from our transgenic mouse model of PTC were compared to human material. The analyses were performed taking into account not only the BRAF mutation but also other PTC initiating events including RET rearrangements and RAS poin mutations. Morover the microarray data were validated with the QPCR reaction.
2015-12-31 | E-GEOD-58545 | biostudies-arrayexpress