A5025976398- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Head and Neck Cancer Studies
- Genomics and Chromatin Dynamics
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- RNA modifications and cancer
- Lung Cancer Research Studies
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- Radiomics and Machine Learning in Medical Imaging
- Lung Cancer Diagnosis and Treatment
- Gene expression and cancer classification
- Epigenetics and DNA Methylation
- BRCA gene mutations in cancer
- AI in cancer detection
- Cancer Diagnosis and Treatment
- Head and Neck Surgical Oncology
- Marine Ecology and Invasive Species
- Immunodeficiency and Autoimmune Disorders
- RNA Research and Splicing
- Coral and Marine Ecosystems Studies
- Molecular Biology Techniques and Applications
- 3D Printing in Biomedical Research
Heidelberg University
2022-2025
University Hospital Heidelberg
2022-2025
German Center for Lung Research
2024
Vienna Biocenter
2022-2023
Research Institute of Molecular Pathology
2022-2023
Aristotle University of Thessaloniki
2016
Homologous repair deficiency (HRD) is present in many cancer types at variable prevalence and can indicate response to platinum-based chemotherapy PARP inhibition. We developed a tumor classification system based on the loss of function genes homologous recombination (HRR) pathway. To this end, somatic germline alterations BRCA1/2 140 other HRR were included assessed for impact gene function. Additionally, information allelic hit type BRCA1 promoter hypermethylation was included. The HRDsum...
Abstract Background The prognostic significance of tumour budding (TB) and minimal cell nest size (MCNS) was shown in human papillomavirus (HPV)-negative head neck squamous carcinomas (HNSCC). However, the optimisation cutpoints, impact HPV-positive HNSCC, comparison with other histopathological grading systems are insufficiently investigated. Methods TB MCNS were analysed digitally 1 10 high-power fields (HPF) 331 HPV-negative cases from TCGA. Optimising cutpoints a new cellular...
Abstract Homologous recombination deficiency (HRD) leads to DNA double‐strand breaks and can be exploited by the use of poly (ADP‐ribose) polymerase (PARP) inhibitors induce synthetic lethality. Extending original therapeutic concept, role HRD is currently being investigated in clinical trials testing immune checkpoint blockers alone or combination with PARP inhibitors, but relationship between cell context cancer incompletely understood. We analyzed association composition, gene expression,...
Abstract Tumor budding (TB) is a prognostic biomarker in HPV-negative and HPV-positive head neck squamous cell carcinoma (HNSCC). Analyzing TCGA CPTAC mutation, RNA, RPPA data performing proteomics IHC two independent in-house cohorts, we uncovered molecular correlates of TB an unprecedentedly comprehensive manner. NSD1 mutations were associated with lower HNSCC. Comparing nonbudding tumors, 66 miRNAs, including the miRNA-200 family, differentially expressed 3,052 (HPV-negative HNSCC) 360...
Abstract Background Recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC) is a severe, frequently lethal condition. Oncogene addiction to epidermal growth factor receptor (EGFR) hallmark of HNSCC, but the clinical efficacy EGFR-targeted therapies remains low. Understanding molecular networks governing EGFR-driven progression paramount exploration (co)-treatment targets predictive markers. Methods We performed function-based mapping differentially expressed genes in...
The checklist of Greek Cyanobacteria was created in the framework Taxon Information System (GTIS), an initiative LifeWatchGreece Research Infrastructure (ESFRI) that has resumed efforts to compile a complete species reported from Greece. This list exhaustive search scientific literature last 60 years. All records taxa known occur Greece were taxonomically updated.The comprises 543 species, classified 130 genera, 41 families, and 8 orders. orders Synechococcales Oscillatoriales have highest...
Abstract Background We aimed to validate the prognostic significance of tumor budding (TB) in p16-positive oropharyngeal squamous cell carcinomas (OPSCC). Methods analyzed digitized H&E-stained slides from a multicenter cohort five large university centers consisting n = 275 cases OPSCC. evaluated TB along with other histological parameters (morphology, tumor-stroma-ratio, lymphovascular invasion (LVI), perineural invasion) and calculated survival outcomes using both univariate...
TP53 is the most frequently mutated gene in human cancer. While no TP53-targeting drugs have been approved USA or Europe so far, preclinical and clinical studies are underway to investigate targeting of specific all mutations, for example, by restoration functionality (TP53mut) protecting wildtype (TP53wt) from negative regulation. We performed a comprehensive mRNA expression analysis 24 cancer types TCGA extract (i) consensus signature shared across mutation types, (ii) differential...
The molecular characterization of endometrial endometrioid adenocarcinomas has provided major advances in its prognostic stratification. However, risk assessment microsatellite instability (MSI) and copy-number (CN)-low cases remains a challenge. Thus, we aimed to identify tissue-based morphologic biomarkers that might help the stratification these cases. Histomorphologic parameters (WHO grading, tumor budding (TB), tumor–stroma ratio (as quantitative description stromal desmoplasia),...
Targeted tumor only sequencing has become a standard practice in cancer diagnostics. This study aims to develop an approach for robust copy number variant (CNV) calling samples using off-target region (OTR) reads. We also established clinical use case homologous recombination deficiency (HRD) score estimation (HRDest) the sum of telomeric allelic imbalance (TAI) and large-scale state transitions (LST) scores without need loss heterozygosity (LOH) information. demonstrated strong correlation...
The adoption of comprehensive genomic profiling in oncology has rapidly increased the demand for standardized tumor sample processing diagnostic laboratories. Automation DNA and RNA library preparation workflows offers possibility to scale-up standardize processing. We report on clinical implementation automated TruSight Oncology 500 High-Throughput workflow from formalin-fixed, paraffin-embedded samples using Biomek i7 hybrid Workstation. Using same input amount, was validated against...
Abstract Somatic hypermutation (SHM) of immunoglobulin variable (V) regions modulates antibody-antigen affinity is initiated by activation-induced cytidine deaminase (AID) on single-stranded DNA (ssDNA). Transcription essential for SHM and AID target genes harbor activating chromatin marks RNA polymerase II (Pol II) stalling, leading to the model that these features favor higher rates mutagenesis. However, whether such relationships exist within V undetermined. Here, we directly compared...
6053 Background: Several studies have demonstrated a negative prognostic impact of tumor cell budding (TCB) in HPV- head and neck squamous carcinoma (HNSCC), but analyses its HPV+ HNSCC the underlying molecular alterations are lacking. Methods: The study cohort included 331 from TCGA with digitalized H&E-stained slides available. Corresponding mutation, methylation, gene expression data were obtained pan-cancer atlas web page. Tumor buds defined as clusters up to four cells separated...
Abstract TP53 mutations are the most common single gene alteration in human cancer with diagnostic and prognostic implications some types. While no TP53-targeting therapeutics have been approved USA or Europe yet, drugs tailored to specific mutations, restoring functionality of mutated (TP53mut), protecting from negative regulation being explored preclinical studies clinical trials. We performed a comprehensive mRNA expression analysis 24 types TCGA extract (i) consensus signature shared...
Targeted tumor only sequencing has become a standard practice in cancer diagnostics. This study aims to develop an approach for robust copy number variant (CNV) calling samples using off-target region (OTR) reads. We also established clinical use case HRD score estimation (HRDest) the sum of allelic imbalance (TAI) and large-scale state transitions (LST) scores without need loss heterozygosity (LOH) information. demonstrated strong correlation between TAI + LST TCGA cohort (R=0.99, p=...
Somatic hypermutation (SHM) of immunoglobulin variable regions in B cells modulates antibody-antigen affinity and is indispensable for adaptive immunity. Mutations are introduced by activation-induced cytidine deaminase (AID) a co-transcriptional manner resulting discrete mutation spectra. Current models propose that activating epigenetic marks, transcriptional pausing convergent transcription necessary optimal AID recruitment. However, whether these or other features can explain the spectra...