Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multiplexed functional genomic analysis of somatic 5' untranslated region mutations across the spectrum of human prostate cancer (Ribosome Profiling)

ABSTRACT: Multiplexed functional genomic analysis of somatic 5' untranslated region mutations across the spectrum of human prostate cancer (Ribosome Profiling)

PROVIDER: PRJNA540298 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Multiplexed functional genomic analysis of somatic 5’ untranslated region mutations across the spectrum of human prostate cancer

Project description:Multiplexed functional genomic analysis of somatic 5’ untranslated region mutations across the spectrum of human prostate cancer

| PRJNA633563 | ENA

Multiplexed functional genomic analysis of somatic 5' untranslated region mutations across the spectrum of human prostate cancer (Ribosome Profiling)

Project description:The functional consequences of cancer patient-derived genetic variants within the 5’ untranslated regions (UTRs) on a genome-wide scale and their effects on mRNA transcript and translation levels are poorly understood. To systematically interrogate the mutational landscape of 5’ UTRs across cancer patients with localized to metastatic disease, we analyzed the genomes of 226 prostate cancer patients and observed thousands of mutations, many of which impact known cis-regulatory elements. We developed a high-throughput multi-layer massively parallel sequencing-based method called PLUMAGE (Pooled full-length UTR Multiplex Assay on Gene Expression) to simultaneously quantify the effects of 545 5’ UTR somatic mutations across recurrently mutated or cancer-related genes from our patient cohort. Our method enabled unprecedented insights into how 5’ UTR mutations can control multiple levels of gene expression simultaneously. In particular, we identified 190 mutations that significantly altered 5’ UTR function, either by creating new DNA binding elements, disrupting known translation regulatory motifs, or simultaneously impacting both transcript levels and mRNA translation. Furthermore, we also determined that 5’ UTR mutations to the MAP kinase signaling pathway are significantly associated with early metastasis. This study is the first to comprehensively interrogate the functional 5’ UTR mutational landscape of a human cancer revealing the importance of untranslated regions in regulating multiple levels of oncogenic gene expression and provides a high-throughput functional genomics solution applicable to many genetically driven diseases.

2021-05-17 | GSE130465 | GEO

Multiplexed functional genomic analysis of somatic 5' untranslated region mutations across the spectrum of human prostate cancer (RNASeq)

Project description:Multiplexed functional genomic analysis of somatic 5' untranslated region mutations across the spectrum of human prostate cancer (RNASeq)

| PRJNA720674 | ENA

Multiplexed functional genomic analysis of somatic 5' untranslated region mutations across the spectrum of human prostate cancer (PLUMAGE)

Project description:Multiplexed functional genomic analysis of somatic 5' untranslated region mutations across the spectrum of human prostate cancer (PLUMAGE)

| PRJNA660556 | ENA

Multiplexed functional genomic analysis of somatic 5’ untranslated region mutations across the spectrum of human prostate cancer (Exome-Seq)

Project description:Multiplexed functional genomic analysis of somatic 5’ untranslated region mutations across the spectrum of human prostate cancer (Exome-Seq)

| PRJNA731519 | ENA

Multiplexed functional genomic analysis of somatic 5' untranslated region mutations across the spectrum of human prostate cancer (PLUMAGE)

2021-05-17 | GSE149487 | GEO

Multiplexed functional genomic analysis of somatic 5’ untranslated region mutations across the spectrum of human prostate cancer (Exome-Seq)

2021-05-20 | GSE174787 | GEO

Multiplexed functional genomic analysis of somatic 5' untranslated region mutations across the spectrum of human prostate cancer (RNASeq)

Project description:The functional consequences of genetic variants within 5’ untranslated regions (UTRs) on a genome-wide scale are poorly understood in disease. We developed a high-throughput multi-layer massively parallel sequencing-based method called PLUMAGE (Pooled full-length UTR Multiplex Assay on Gene Expression) to quantify the molecular consequences of somatic 5’ UTR mutations found across 229 prostate cancer patients with localized to metastatic disease. We show that 5’ UTR mutations can control both transcript levels and mRNA translation rates through the creation of new DNA binding elements or RNA-based cis-regulatory motifs. We also discover that single point mutations can simultaneously impact both transcript levels and mRNA translation of the same gene. Using gene editing technology, we validate that a single point mutation in the oncogenic CKS2 5’ UTR can increase mRNA specific translation. Turning to a molecular pathway critical for cancer, we provide evidence that functional 5’ UTR mutations in the MAP kinase signaling pathway can upregulate pathway-specific gene expression and are associated with distinct clinical outcomes. Our study reveals the diverse mechanisms by which the mutational landscape of 5’ UTRs can co-opt multiple levels of gene expression and demonstrates that single nucleotide alternations within leader sequences are functional in cancer.

2021-05-17 | GSE171729 | GEO

Multiplexed functional genomic analysis of somatic 5’ untranslated region mutations across the spectrum of human prostate cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-05-17 | GSE149489 | GEO

A new cost-effective ribosome profiling technique complements the functional genome annotation and reveals a key role of genic 3’ untranslated region in plant translatomic variation

Project description:A new cost-effective ribosome profiling technique complements the functional genome annotation and reveals a key role of genic 3’ untranslated region in plant translatomic variation

2021-05-30 | PXD026112 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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