Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Clonal selection confers distinct evolutionary trajectories in BRAF-driven cancers

ABSTRACT: Clonal selection confers distinct evolutionary trajectories in BRAF-driven cancers

PROVIDER: PRJNA550100 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Clonal selection confers distinct evolutionary trajectories in BRAF-driven cancers

Project description:Analysis of BRAF variant gene expression activity after constitutive variant expression in immortalized lung ephithelial cells. The hypothesis tested in the present study was that the level of BRAF activity will vary based on the identity of the variant expressed. Results provide important information on the variation and continous quality of BRAF activity across diverse variants that were tested.

2019-10-06 | GSE133151 | GEO

Clonal selection confers distinct evolutionary trajectories in BRAF-driven cancers.

Project description:Molecular determinants governing the evolution of tumor subclones toward phylogenetic branches or fixation remain unknown. Using sequencing data, we model the propagation and selection of clones expressing distinct categories of BRAF mutations to estimate their evolutionary trajectories. We show that strongly activating BRAF mutations demonstrate hard sweep dynamics, whereas mutations with less pronounced activation of the BRAF signaling pathway confer soft sweeps or are subclonal. We use clonal reconstructions to estimate the strength of "driver" selection in individual tumors. Using tumors cells and human-derived murine xenografts, we show that tumor sweep dynamics can significantly affect responses to targeted inhibitors of BRAF/MEK or DNA damaging agents. Our study uncovers patterns of distinct BRAF clonal evolutionary dynamics and nominates therapeutic strategies based on the identity of the BRAF mutation and its clonal composition.

| S-EPMC6853924 | biostudies-literature

A secondary mutation in BRAF confers resistance to RAF inhibition in a BRAF V600E-mutant brain tumor

Project description:A secondary mutation in BRAF confers resistance to RAF inhibition in a BRAF V600E-mutant brain tumor

| PRJNA476392 | ENA

A secondary mutation in BRAF confers resistance to RAF inhibition in a BRAF V600E-mutant brain tumor

Project description:A secondary mutation in BRAF confers resistance to RAF inhibition in a BRAF V600E-mutant brain tumor

| PRJNA476393 | ENA

Loss of Stag2/Stag3 confers resistance to BRAF inhibition in melanoma

Project description:Loss of Stag2/Stag3 confers resistance to BRAF inhibition in melanoma

| PRJEB10951 | ENA

HDX-MS data on bRaf, bRaf/Cdc37 and bRaf/Cdc37/Hsp90 protein complexes

Project description:HDX-MS data on bRaf, bRaf/Cdc37 and bRaf/Cdc37/Hsp90 protein complexes

2022-01-04 | MSV000088635 | MassIVE

Deep Sequencing Identifies Multiple Fusion Transcripts, Differentially Expressed Genes, and Generalized Immune Suppression in BRAF (V600E) mutant vs. BRAF wild-type Papillary Thyroid Carcinoma

Project description:CONTEXT: BRAF V600E mutation (BRAF-mut.) confers aggressiveness in papillary thyroid carcinoma, but unidentified genomic abnormalities may be required for full phenotypic expression. OBJECTIVE: To perform deep sequencing to identify genes differentially expressed between BRAF-mut. and BRAF-wild-type (BRAF-WT) tumors, and to compare to patient clinical status. DESIGN: BRAF-mut. and BRAF-WT tumors were identified in patients with T1N0 and with T23N1 tumors. Expression levels of genes were determined from RNA sequencing (RNA-Seq) data and fusion transcripts were detected. NanoString was used to validate the RNA-Seq data for immune genes. SETTING: Patients were seen at two sites of a major referral medical center. PATIENTS: Twenty patients were studied. BRAF-mut. patients included 9 women, 3 men; 9 were TNM stage I and 3 were stage III; 3 (25%) had lymphocytic thyroiditis. BRAF-WT included 5 women; 3 men; all were stage I; 5 (62.5%) had lymphocytic thyroiditis. RESULTS: 560 of 13,085 genes were differentially expressed by RNA-Seq, and MetaCore analysis identified 55 immune function genes that were differentially expressed as a function of BRAF mutational status. Immune function genes were broadly underexpressed in BRAF-mut. tumors, with only 4 genes (HLA-G, CXCL14, TIMP1, IL1RAP) more highly expressed. NanoString validated the RNA Seq data for immune genes. Eleven high confidence fusion transcripts were detected, four being inter-chromosomal and seven intra-chromosomal. CONCLUSION: BRAF-mut. papillary thyroid cancers have less expression of immune and inflammatory response genes than BRAF-WT tumors. Thirteen of 20 (65%) tumors had between one and three fusion transcripts. Functional studies will be required to determine the potential role of the newly identified genomic abnormalities in contributing to the aggressiveness of BRAF-mut. and wild-type tumors. RNA-seq was performed on 20 thyroid carcinoma tumors

2015-07-01 | E-GEOD-48953 | biostudies-arrayexpress

Unique evolutionary trajectories of breast cancers with distinct genomic and spatial heterogeneity

Project description:Unique evolutionary trajectories of breast cancers with distinct genomic and spatial heterogeneity

| PRJNA722657 | ENA

Deep Sequencing Identifies Multiple Fusion Transcripts, Differentially Expressed Genes, and Generalized Immune Suppression in BRAF (V600E) mutant vs. BRAF wild-type Papillary Thyroid Carcinoma

2015-07-01 | GSE48953 | GEO

Divergent clonal differentiation trajectories of T cell exhaustion (scATAC-seq)

Project description:T cells activated by chronic antigen exposure in the setting of viral infections or cancer can adopt an exhausted T cell (TEx) state, characterized by reduced effector function and proliferative capacity, and the upregulation of inhibitory receptors. Here, we generate a single-cell multi-omic atlas of T cell exhaustion in chronic viral infection that redefines the phenotypic diversity and molecular regulation of TEx states. Longitudinal analysis of the T cell response identifies an early effector phenotype that is epigenetically primed for TEx differentiation. However, clonal T cell trajectories defined using paired single-cell RNA and T cell receptor (scRNA/TCR-seq) sequencing reveal divergent differentiation trajectories among clones that recognize shared antigens, resulting in TEx- or effector memory-biased clone behaviors. Multi-organ clonal analysis reveals that T cell clone behaviors are sensitive to the tissue environment, and the liver niche preclude the development of effector memory phenotypes and induce exaggerated exhaustion. Finally, we show that divergent clonal trajectories are driven by differences in TCR affinity, and that high-affinity T cell clones preferentially adopt the divergent fate, while low-affinity clones adopt effector memory fates that are deleted in high antigen niches. These findings reveal heterogeneity in clonal T cell responses to chronic antigen and link TCR signal strength and epigenetic programming to TEx cell fates and persistence, which may be manipulated for cancer immunotherapy.

2022-07-25 | GSE188669 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data