Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE21032phs000310.v1.p1
PROVIDER: PRJNA74907 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Discovery of Non-ETS Gene Fusions in Human Prostate Cancer using Next Generation RNA Sequencing
| PRJNA74905 | ENA
Project description:<p>Half of prostate cancers harbor gene fusions between <i>TMPRSS2</i> and members of the <i>ETS</i> transcription factor family. To date little is known about the presence of non-ETS fusion events in prostate cancer. We employed next-generation transcriptome sequencing (RNA-Seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes <i>ETV1</i> and <i>ERG</i>, and five involving non-ETS genes such as <i>CDKN1A</i> (p21), <i>CD9</i> and <i>IKBKB</i> (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene <i>RSRC2</i>. The novel gene fusions are found to be of low frequency but interestingly, the non-ETS fusions were all present in prostate cancer harboring the <i>TMPRSS2-ERG</i> gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement prone phenotype.</p>
| phs000310 | dbGaP
Project description:Recent studies including next-generation sequencing have identified genomic events in prostate cancer including ETS gene fusions. However, it is critical to identify druggable targets for prostate cancer and their mechanism of action for therapeutic intervention. Here, we show that prolyl 4-hydroxylase, alpha polypeptide I (P4HA1) is overexpressed in aggressive prostate cancer and amplified in a subset of metastatic prostate cancer. This study provides mechanistic insights of P4HA1 regulation and its mode of action including its role in regulating MMP1. Importantly, P4HA1 mediated invasion in cancer cells could be reversed using MMP1 inhibitor, revealing therapeutic utility of targeting P4HA1 either directly or by inhibiting its downstream effectors. Two-color experiment, in duplicates.
2015-05-10 | E-GEOD-55787 | biostudies-arrayexpress
Project description:Recent studies including next-generation sequencing have identified genomic events in prostate cancer including ETS gene fusions. However, it is critical to identify druggable targets for prostate cancer and their mechanism of action for therapeutic intervention. Here, we show that prolyl 4-hydroxylase, alpha polypeptide I (P4HA1) is overexpressed in aggressive prostate cancer and amplified in a subset of metastatic prostate cancer. This study provides mechanistic insights of P4HA1 regulation and its mode of action including its role in regulating MMP1. Importantly, P4HA1 mediated invasion in cancer cells could be reversed using MMP1 inhibitor, revealing therapeutic utility of targeting P4HA1 either directly or by inhibiting its downstream effectors.
2015-05-10 | GSE55787 | GEO
Project description:Next Generation Sequencing technologies have enabled de novo gene fusion discovery that could reveal candidates with therapeutic significance in cancer. Here we present an open-source software package, ChimeraScan, for the discovery of chimeric transcription between two independent transcripts. Three cancer cell lines with known gene fusions
2011-09-01 | E-GEOD-29098 | biostudies-arrayexpress
Project description:<p>Half of prostate cancers harbor gene fusions between <i>TMPRSS2</i> and members of the <i>ETS</i> transcription factor family. To date little is known about the presence of non-ETS fusion events in prostate cancer. We employed next-generation transcriptome sequencing (RNA-Seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes <i>ETV1</i> and <i>ERG</i>, and five involving non-ETS genes such as <i>CDKN1A</i> (p21), <i>CD9</i> and <i>IKBKB</i> (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene <i>RSRC2</i>. The novel gene fusions are found to be of low frequency but interestingly, the non-ETS fusions were all present in prostate cancer harboring the <i>TMPRSS2-ERG</i> gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement prone phenotype.</p>
| phs000310.v1.p1 | EGA
Project description:Approximately 50% of prostate cancers have chromosomal translocations resulting in the over-expression one of four ETS family transcription factors. However, it is not known why these four four family members are selected for oncogenic roles, while other ETS proteins are not. We found that the four oncogenic ETS family members have a specific role in prostate cell migration. Using chromatin immunoprecipitation coupled with next-generation sequencing, this specific biological function was matched to a specific set of genomic targets highlighted by the presence of an AP-1 binding site. ETS/AP-1 binding sites are prototypical Ras-responsive elements, but oncogenic ETS proteins could activate a Ras/MAPK transcriptional program in the absence of MAPK activation. These findings indicate that the specific function of ETS proteins over-expressed in prostate cancer is the activation of a Ras/MAPK gene expression program in the absence of signaling pathway mutations. ChIP sequencing two transcription factors in PC3 cells, four transcription factors plus a FLAG control in RWPE-1 cells and input DNA sequencing from each cell line.
2011-10-19 | E-GEOD-29808 | biostudies-arrayexpress
Project description:Approximately 50% of prostate cancers have chromosomal translocations resulting in the over-expression one of four ETS family transcription factors. However, it is not known why these four four family members are selected for oncogenic roles, while other ETS proteins are not. We found that the four oncogenic ETS family members have a specific role in prostate cell migration. Using chromatin immunoprecipitation coupled with next-generation sequencing, this specific biological function was matched to a specific set of genomic targets highlighted by the presence of an AP-1 binding site. ETS/AP-1 binding sites are prototypical Ras-responsive elements, but oncogenic ETS proteins could activate a Ras/MAPK transcriptional program in the absence of MAPK activation. These findings indicate that the specific function of ETS proteins over-expressed in prostate cancer is the activation of a Ras/MAPK gene expression program in the absence of signaling pathway mutations.
2011-10-19 | GSE29438 | GEO
Project description:Approximately 50% of prostate cancers have chromosomal translocations resulting in the over-expression one of four ETS family transcription factors. However, it is not known why these four four family members are selected for oncogenic roles, while other ETS proteins are not. We found that the four oncogenic ETS family members have a specific role in prostate cell migration. Using chromatin immunoprecipitation coupled with next-generation sequencing, this specific biological function was matched to a specific set of genomic targets highlighted by the presence of an AP-1 binding site. ETS/AP-1 binding sites are prototypical Ras-responsive elements, but oncogenic ETS proteins could activate a Ras/MAPK transcriptional program in the absence of MAPK activation. These findings indicate that the specific function of ETS proteins over-expressed in prostate cancer is the activation of a Ras/MAPK gene expression program in the absence of signaling pathway mutations.
2011-10-20 | GSE29808 | GEO
Project description:Approximately 50% of prostate cancers have chromosomal translocations resulting in the over-expression one of four ETS family transcription factors. However, it is not known why these four four family members are selected for oncogenic roles, while other ETS proteins are not. We found that the four oncogenic ETS family members have a specific role in prostate cell migration. Using chromatin immunoprecipitation coupled with next-generation sequencing, this specific biological function was matched to a specific set of genomic targets highlighted by the presence of an AP-1 binding site. ETS/AP-1 binding sites are prototypical Ras-responsive elements, but oncogenic ETS proteins could activate a Ras/MAPK transcriptional program in the absence of MAPK activation. These findings indicate that the specific function of ETS proteins over-expressed in prostate cancer is the activation of a Ras/MAPK gene expression program in the absence of signaling pathway mutations. 16 samples were analyzed, comprised of four replicates each of four different biological conditions. RNA from U0126 treated RWPE-1 empty vector cell RNA serves as a control for each experiment. Cell lines have retroviral expression constructs expressing either empty vector, Flag-ERG, or Flag-ETV1.
2011-10-18 | E-GEOD-29438 | biostudies-arrayexpress