Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of hypermutation and defective mismatch repair in ctDNA from metastatic prostate cancer

ABSTRACT: DNA mismatch repair defects (MMRd) and tumor hypermutation are rare and under-characterized in metastatic prostate cancer. Furthermore, since hypermutated MMRd prostate cancers can respond to immune checkpoint inhibitors, there is an urgent need for practical detection tools. We analyzed cell-free DNA targeted sequencing data from 434 metastatic prostate cancer patients with circulating tumor DNA (ctDNA) purity above 2%. Samples with somatic hypermutation were subjected to 150x whole exome sequencing. These data allowed us to interrogate the salient genomic properties of this rare prostate cancer subtype and correlate findings with patient clinical outcomes.

PROVIDER: EGAS00001003899 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Patterns of hypermutation shape gliomagenesis and immunotherapy response in mismatch repair deficient glioma

Project description:Primary mismatch-repair deficient (priMMRD) gliomas are lethal tumours characterized by hypermutation, resistance to chemoradiation, and variable response to immunotherapy.To investigate the mechanisms governing the emergence of driver mutations and their impact on gliomagenesis and outcome, we analyzed genomic and clinical data of 162 priMMRD gliomas. We identified three subgroups defined by secondary driver mutations in replicative DNA polymerases or IDH1. These subgroups converge on glioma drivers through distinct combinations of genomic instability-generating mechanisms, displaying an inverse correlation between point mutation and copy number alteration. MMRD signaturesdrive the emergence of specific mutations in TP53 and IDH1, notably excluding common pediatric glioma drivers. Global hypomethylation stratifies priMMRD gliomas into a unique methylation cluster. DNA-polymerasemut priMMRD gliomas exhibit ultrahypermutation, an immune-hot microenvironment, and immunotherapy responsiveness, whereas IDH1mut priMMRD gliomas are immune-cold and immunotherapy resistant. MMRD-driven gliomagenesis defines the role of non-random mutagenesis-patterns in cancer development, providing frameworks for targeted and immune-therapeutics.

2025-10-09 | GSE307219 | GEO

UNG shapes the specificity of AID-induced somatic hypermutation

Project description:This SuperSeries is composed of the following subset Series: GSE39108: UNG shapes the specifity of AID-induced somatic hypermutation in non B cells GSE39114: UNG shapes the specifity of AID-induced somatic hypermutation in B cells Refer to individual Series

2012-07-04 | E-GEOD-39115 | biostudies-arrayexpress

Integrated multi-omics assessment of lineage plasticity features in a prostate cancer patient with brain and dural metastases

Project description:Metastasis to the brain is rare in prostate cancer and unfortunately, incredibly lethal. We evaluated the tissue biopsies of a patient with a treatment-induced metastatic lesion to the brain of the neuroendocrine prostate cancer (NEPC) subtype. We performed genomic, transcriptomic, and proteomic characterization on the primary prostate tumor, the metastatic brain NEPC, and an additional metastatic nodule in the dura with adenocarcinoma histology. These data are the proteomics result of this patient, with three replicates for each sample (primary prostate, dura adenocarcinoma, brain NEPC).

2024-06-12 | MSV000095007 | MassIVE

Expression of the cancer-associated DNA polymerase epsilon P286R in fission yeast leads to translesion polymerase dependent hypermutation and defective DNA replication

Project description:Somatic mutations in the proofreading domain of the replicative DNA polymerase epsilon (POLE-exonuclease domain mutations, POLE-EDMs) are frequently found in colorectal and endometrial cancers and, occasionally, in other tumours. POLE-associated cancers typically display hypermutation, microsatellite stability and a unique mutational signature, with predominance of C > A transversions in the context TCT. To understand better the contribution of hypermutagenesis to tumour development, we have modelled the most recurrent POLE-EDM (POLE-P286R) in Schizosaccharomyces pombe. Whole-genome sequencing analysis revealed that the corresponding pol2-P287R also has a strong mutator effect in vivo, with high frequency of base substitutions and relatively few frameshift mutations. The mutations are equally distributed across different genomic regions, but they occur within an AT-rich context. The most abundant mutations are TCT > TAT transversions and, in contrast to human, TCG > TTG transitions are not elevated, likely due to the absence of cytosine methylation in fission yeast. The high mutation burden of pol2-P287R leads to increased sensitivity to elevated dNTP levels and DNA damaging agents and a phenotype that is exacerbated by depletion of the Pfh1 helicase. In addition, S phase is aberrant and RPA foci are elevated, suggestive of persistent ssDNA or DNA damage, and pol2-P287R shows synthetic lethality with rad3 deletion, indicative of checkpoint activation. Significantly, deletion of translesion polymerases kappa and eta partially suppresses pol2-P287R hypermutation, indicating that both enzymes contribute to this phenotype.

2021-06-11 | GSE169231 | GEO

Pembrolizumab in MMR-Proficient Metastatic Colorectal Cancer Pharmacologically Primed to Trigger Hypermutation Status

Project description:In this study, MMRd metastatic colorectal cancer (mCRC) patients who failed standard therapies will undergo treatment with pembrolizumab, while RAS-extended mutated MMR-proficient mCRC patients will be tested for o6-methylguanine-DNA-methyltransferase (MGMT) expression (IHC) and then for MGMT promoter methylation. MGMT IHC-negative, promoter methylation positive patients will be treated with temozolomide (TMZ). Patients progressing under temozolomide will be tested for tumor mutational burden (TMB) and proceed to pembrolizumab if TMB is > 20 mutations/Mb. The primary study hypothesis is that tumors with acquired resistance to temozolomide become hypermutated and are sensitive to pembrolizumab.

| 2272487 | ecrin-mdr-crc

Restoring the potency of neutralizing antibody via guided hypermutation with hyper-antibody editor

Project description:Somatic hypermutation (SHM) drives antibody affinity maturation in B cells, and mimicking this process has advanced therapeutic antibody development. Unlike conventional base editing, antibody diversification requires diverse mutations within the antibody complementary determining region (CDR) loops. Here, we engineered a hyper-antibody editor, HAE1, by integrating cytosine and adenine deaminases with a nicked, PAMless Cas9 variant, SpRY. HAE1 enables broad-spectrum mutagenesis with unrestricted targeting, fully covering mutation types observed in nature. Moreover, we developed a dual-expression system in mammalian cells that allows simultaneous expression of both transmembrane and secreted full-length antibodies, streamlining mutation, selection, and validation within the same cells. Using this platform, we rejuvenated the SARS-CoV-2 antibody CV07-209, restoring potency against Omicron variants. These results demonstrate the effectiveness of HAE1 as a powerful tool for antibody engineering, offering a practical strategy for evolving antibodies to address rapidly mutating pathogens and other therapeutic challenges.

2025-12-06 | GSE281195 | GEO

Patterns of hypermutation shape gliomagenesis and immunotherapy response in mismatch repair deficient glioma

Project description:Patterns of hypermutation shape gliomagenesis and immunotherapy response in mismatch repair deficient glioma

| PRJNA1314779 | ENA

Restoring the potency of neutralizing antibody via guided hypermutation with hyper-antibody editor [Antibody_sequencing]

2025-12-06 | GSE281292 | GEO

human HG-3 B-lymphome cell line subclones

Project description:Genetic heterogeneity though common in tumors has been rarely documented in cell lines. To examine how often B-lymphoma cell lines are comprised of subclones, we performed immunoglobulin (Ig) heavy chain hypermutation analysis. Revealing that subclones are not rare in B-cell lymphoma cell lines, 6/49 Ig hypermutated cell lines (12%) consisted of subclones with individual Ig mutations. Subclones were also identified in 2/284 leukemia/lymphoma cell lines exhibiting bimodal CD marker expression. We successfully isolated 10 subclones from four cell lines HG3, SU-DHL-5, TMD-8, U-2932). Whole exome sequencing was performed to molecularly characterize these subclones. We in detail describe the clonal structure of cell line HG3, derived from chronic lymphocytic leukemia. HG3 consists of three lineages each bearing clone-specific aberrations, gene expression and DNA methylation patterns. While donor patient leukemic cells were CD5+ , two of three HG3 subclones had independently lost this marker. CD5 on HG3 cells was regulated by epigenetic/transcriptional mechanisms rather than by alternative splicing as reported hitherto. In conclusion, we show that the presence of subclones in cell lines carrying individual mutations and characterized by sets of differentially expressed genes is not uncommon. We show also that these subclones can be useful isogenic models for regulatory and functional studies.

2016-09-30 | E-MTAB-4955 | biostudies-arrayexpress

human SU-DHL-5 and TMD-8 B-lymphome cell line subclones

Project description:Genetic heterogeneity though common in tumors has been rarely documented in cell lines. To examine how often B-lymphoma cell lines are comprised of subclones, we performed immunoglobulin (Ig) heavy chain hypermutation analysis. Revealing that subclones are not rare in B-cell lymphoma cell lines, 6/49 Ig hypermutated cell lines (12%) consisted of subclones with individual Ig mutations. Subclones were also identified in 2/284 leukemia/lymphoma cell lines exhibiting bimodal CD marker expression. We successfully isolated 10 subclones from four cell lines HG3, SU-DHL-5, TMD-8, U-2932). Whole exome sequencing was performed to molecularly characterize these subclones. We in detail describe the clonal structure of cell line HG3, derived from chronic lymphocytic leukemia. HG3 consists of three lineages each bearing clone-specific aberrations, gene expression and DNA methylation patterns. While donor patient leukemic cells were CD5+, two of three HG3 subclones had independently lost this marker. CD5 on HG3 cells was regulated by epigenetic/transcriptional mechanisms rather than by alternative splicing as reported hitherto. In conclusion, we show that the presence of subclones in cell lines carrying individual mutations and characterized by sets of differentially expressed genes is not uncommon. We show also that these subclones can be useful isogenic models for regulatory and functional studies.

2016-09-30 | E-MTAB-4956 | biostudies-arrayexpress

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