2 research outputs found
Methylome analyses of three glioblastoma cohorts reveal chemotherapy sensitivity markers within DDR genes
Background: Gliomas evade current therapies through primary and acquired resistance and the effect of temozolomide is mainly restricted to methylguanin-O6-methyltransferase promoter (MGMT) promoter hypermethylated tumors. Further resistance
markers are largely unknown and would help for better stratification.
Methods: Clinical data and methylation profiles from the NOA-08 (104, elderly
glioblastoma) and the EORTC 26101 (297, glioblastoma) studies and 398 patients
with glioblastoma from the Heidelberg Neuro-Oncology center have been analyzed
focused on the predictive effect of DNA damage response (DDR) gene methylation.
Candidate genes were validated in vitro.
Results: Twenty-eight glioblastoma 5'-cytosine-phosphat-guanine-3' (CpGs) from
17 DDR genes negatively correlated with expression and were used together with
telomerase reverse transcriptase (TERT) promoter mutations in further analysis.
CpG methylation of DDR genes shows highest association with the mesenchymal
(MES) and receptor tyrosine kinase (RTK) II glioblastoma subgroup. MES tumors
have lower tumor purity compared to RTK I and II subgroup tumors. CpG hypomethylation of DDR genes TP73 and PRPF19 correlated with worse patient survival
in particular in MGMT promoter unmethylated tumors. TERT promoter mutation is
most frequent in RTK I and II subtypes and associated with worse survival. Primary
glioma cells show methylation patterns that resemble RTK I and II glioblastoma and
long term established glioma cell lines do not match with glioblastoma subtypes.
Silencing of selected resi
Automated quantitative tumour response assessment of MRI in neuro-oncology with artificial neural networks: a multicentre, retrospective study
Background The Response Assessment in Neuro-Oncology (RANO) criteria and requirements for a uniform protocol
have been introduced to standardise assessment of MRI scans in both clinical trials and clinical practice. However