Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single Patient BRAF Mutant Brain Tumor, Pre- and Post-dabrafenib WES.

ABSTRACT:

A single adolescent patient with a BRAF V600E mutated brain tumor was treated with dabrafenib and had a complete response, followed by progression. The pre-treatment and post-progression tumors were both sequenced in order to identify potential drivers of resistance.

PROVIDER: phs001629 | dbGaP |

REPOSITORIES: dbGaP

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	GapExchange_phs001629.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001629.BRAF_V600E.v1.p1.MULTI.pdf	Pdf
	manifest_phs001629.BRAF_V600E.v1.p1.c1.GRU-IRB-PUB.pdf	Pdf
	datadict_v2.xsl	Other

Items per page:

1 - 5 of 15

Similar Datasets

DNA Seq data: biopy samples from patients pre- and post- treated with Vorinostat

Project description:BRAF(V600E) mutant melanomas treated with inhibitors of the BRAF and MEK kinases almost invariably develop resistance, which is frequently caused by reactivation of the Mitogen Activated Protein Kinase (MAPK) pathway. To identify novel treatment options for such patients, we searched for acquired vulnerabilities of MAPK inhibitor-resistant melanomas. We find that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the histone deacetylase inhibitor (HDACi) vorinostat represses SLC7A11 that leads to a lethal increase in the already elevated levels of ROS in drug-resistant cells, thereby causing selective apoptotic death of only the drug resistant tumor cells. Consistently, treatment of BRAF inhibitor-resistant melanoma with HDACi in mice results in a dramatic tumor regression. In a study in patients with advanced BRAF+MEK inhibitor resistant melanoma, we find that HDACi can selectively ablate drug-resistant tumor cells, providing clinical proof of concept for the novel therapy identified here. DNA Seq data: biopy samples from patients pre- and post- treated with Vorinostat; check mutations related to MAPKi-resistance

2018-04-18 | GSE111140 | GEO

Mapping heterogeneity in a patient-derived melanoma culture by single-cell RNA-seq

Project description:Recent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma. Gene expression modules had prognostic relevance when compared with gene expression data from published melanoma samples and patient survival data. We surveyed kinome expression patterns across sub-populations of the BRAF/NRAS wild type sample and found that CDK4 and CDK2 were consistently highly expressed in the majority of cells, suggesting that these kinases might be involved in melanoma progression. Treatment of cells with the CDK4 inhibitor palbociclib restricted cell proliferation to a similar, and in some cases greater, extent than MAPK inhibitors. Finally, we identified a low abundant sub-population in this sample that highly expressed a module containing ABC transporter ABCB5, surface markers CD271 and CD133, and multiple aldehyde dehydrogenases (ALDHs), as markers for melanoma stem or initiating cells. Patient-derived cultures of the BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant metastases showed more homogeneous single-cell gene expression patterns with gene expression modules for proliferation and ABC transporters. Taken together, our results describe an intertumor and intratumor heterogeneity in melanoma short-term cultures which might be relevant for patient survival, and suggest promising targets for new treatment approaches in melanoma therapy.

2017-01-12 | GSE81383 | GEO

RNA Seq data: A375, A375R, A375DR vorinostat treated, and biopy samples from patients pre- and post- treated with Vorinostat

2018-04-18 | GSE110948 | GEO

Pre- and post-surgery brain tumor multimodal magnetic resonance imaging data optimized for large scale computational modelling.

Project description:We present a dataset of magnetic resonance imaging (MRI) data (T1, diffusion, BOLD) acquired in 25 brain tumor patients before the tumor resection surgery, and six months after the surgery, together with the tumor masks, and in 11 controls (recruited among the patients' caregivers). The dataset also contains behavioral and emotional scores obtained with standardized questionnaires. To simulate personalized computational models of the brain, we also provide structural connectivity matrices, necessary to perform whole-brain modelling with tools such as The Virtual Brain. In addition, we provide blood-oxygen-level-dependent imaging time series averaged across regions of interest for comparison with simulation results. An average resting state hemodynamic response function for each region of interest, as well as shape maps for each voxel, are also contributed.

| S-EPMC9637199 | biostudies-literature

Comparing pre-operative versus post-operative single and multi-fraction stereotactic radiotherapy for patients with resectable brain metastases.

Project description:BackgroundThe standard treatment for patients with large brain metastases and limited intracranial disease is surgical resection and post-operative stereotactic radiosurgery (SRS). However, post-operative SRS still has elevated rates of local failure (LF) and is complicated by radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated therapy may improve local control through delivering a higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) will have less toxicity compared to patients who receive post-operative SRS or FSRT.MethodsA multi-institutional analysis was conducted and included patients who had surgical resection and stereotactic radiation therapy to treat at least one brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined as patients with one of the following adverse events: 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN.Results279 patients were eligible for analysis. The median follow-up time was 9 months. 87 % of patients received fractionated treatment. 29 % of patients received pre-operative treatment. The composite endpoint incidences for post-operative SRS (n = 10), post-operative FSRT (n = 189), pre-operative SRS (n = 27), and pre-operative FSRT (n = 53) were 0 %, 17 %, 15 %, and 7.5 %, respectively.ConclusionsIn our study, the composite endpoint of 7.5% for pre-operative FSRT compares favorably to our post-operative FSRT rate of 17%. Pre-operative FSRT was observed to have low rates of LF, MD, and RN. Prospective validation is needed.

| S-EPMC9676204 | biostudies-literature

Single-cell analysis reveals inter- and intra-tumor heterogeneity in metastatic breast cancer

Project description:The plasticity and heterogeneity of cancer cells are known to play a major role in malignant progression, yet the precise molecular drivers of metastases remain elusive. We performed single-cell RNA-Seq (scRNA-Seq) on tumours and matched lung macrometastases of patient-derived xenografts (PDXs) of breast cancer to identify molecular mechanisms of metastasis during colonization.

2022-05-13 | GSE202695 | GEO

MiRNA 3’ ends shorten during adolescent brain maturation

Project description:MicroRNA (miRNA) dysregulation is well-documented in psychiatric disease, but miRNA dynamics during adolescent and early adult brain maturation, when symptoms first appear for many of these diseases, remain poorly understood. Here, we use RNA sequencing to examine miRNAs and their mRNA targets in cortex and hippocampus from early, mid-, and late adolescent and adult mice. We also use Quantitative Proteomics by tandem mass tag mass spectrometry (TMT-MS) to examine protein dynamics in cortex from the same subjects.

2023-02-17 | PXD040229 | Pride

A biobank of patient-derived pediatric brain tumor models

Project description:Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new treatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children’s Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic xenograft models and 7 cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic xenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.

| EGAS00001002536 | EGA

Integrated data analysis reveals distinct drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

Project description:Multiple joint data, including methylome, transcriptomic, BRAF V600E mutation results and clinical features, aiming to identify molecular drivers in papillary thyroid carcinomas.

2017-05-04 | GSE86961 | GEO

Whole-exome sequencing of genomic DNA extracted from patient-derived melanoma cell lines resistant to vemurafenib (PLX).

Project description:Whole-exome sequencing was performed on DNA sample extracted from one melanoma cell line resistant to vemurafenib (BRAF V600E inhibitor). The aim of the experiment was to search for genetic alterations responsible for phenotypic diversity of melanoma cell lines reported at the level of cell morphology, activity of signaling pathways essential for melanoma development and progression, and resistance to targeted therapeutics.

2019-07-25 | E-MTAB-8150 | biostudies-arrayexpress