Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer [Expression]

ABSTRACT: Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer [Expression]

PROVIDER: PRJNA900161 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer

Project description:Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer

| PRJNA900156 | ENA

Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer [Methylation]

Project description:Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer [Methylation]

| PRJNA900160 | ENA

Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer [Expression]

Project description:High grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency, and while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multi-omics approach to interrogate the molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means. We also observed frequent whole genome duplication, and global changes in immune composition with evidence of immune escape. This analysis highlights diverse evolutionary changes within HGSC that conspire to evade therapy and ultimately overwhelm individual patients.

2022-11-12 | GSE217672 | GEO

Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer [Methylation]

2022-11-12 | GSE217673 | GEO

The molecular landscape of homologous recombination deficient, end-stage, high grade serous ovarian cancer

Project description:High grade serous cancer (HGSC) is frequently characterizsed by homologous recombination (HR) DNA repair deficiency, and while most such tumours are sensitive to initial treatment, acquired resistance is common. We undertook a multi-omics approach to interrogating mechanisms of resistance, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. We observed frequent reversion mutations, resistance mechanisms restoring HR by other means, a high frequency of whole-genome duplication (WGD) suggestive of an evolutionary advantage, and global changes in immune composition with evidence of immune escape. Collectively these findings have implications for therapeutic intervention for HR-deficient HGSC.

2023-02-27 | PXD030034 | Pride

Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer

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

2022-11-12 | GSE217674 | GEO

SETMAR functions in illegitimate DNA recombination and non-homologous end joining repair

Project description:SETMAR functions in illegitimate DNA recombination and non-homologous end joining repair

| PRJNA533076 | ENA

53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination (END-seq)

Project description:53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination (END-seq)

| PRJNA552570 | ENA

The molecular landscape of homologous recombination deficient, end-stage, high grade serous ovarian cancer

| EGAS00001006789 | EGA

53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination (END-seq)

Project description:53BP1 activity drives genome instability and embryonic lethality in BRCA1-deficient cells by inhibiting homologous recombination (HR).53BP1’s anti-recombinogenic functions require phosphorylation-dependent interactions with two effector complexes, PTIP and RIF1/Shieldin. While RIF1/Shieldin is thought to block 5’-3’ nucleolytic processing of DNA ends, it remains unclear how PTIP antagonizes HR. Here we show that mutation of the PTIP interaction site in 53BP1 (S25A) increases Shieldin association with DNA damage. Despite excessive Shieldin “end-blocking” activity, the mutant protein allows end resection sufficient to rescue the lethality of BRCA1D11 mice. End resection in BRCA1D1153BP1S25A mice is rewired in a manner driven by DNA2 since Shieldin blocks EXO1-mediated nucleolytic processing. Despite ample resection, mutant cells fail to complete HR, as 53BP1/Shieldin also inhibits RNF168-mediated loading of PALB2/RAD51 onto ssDNA post-resection. As a result, BRCA1D1153BP1S25A mice exhibit hallmark features of HR insufficiency, including increased developmental neuronal apoptosis, premature aging and hypersensitivity to PARP inhibitors. Disruption of Shieldin or forced targeting of PALB2 to ssDNA in BRCA1D1153BP1S25A cells restores RNF168 recruitment, RAD51 nucleofilament formation, and PARPi resistance. Our study supports a model in which RIF1/Shieldin and PTIP associate independently with 53BP1 to regulate distinct end-resection pathways, and reveals a critical function of 53BP1/Shieldin post-resection that limits RNF168-mediated loading of RAD51.

2019-10-22 | GSE133806 | GEO

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