Olaf Neumann
A5078175380- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Diagnosis and Treatment
- Tracheal and airway disorders
- Pancreatic and Hepatic Oncology Research
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Tumors and Oncological Cases
- Radiomics and Machine Learning in Medical Imaging
- Voice and Speech Disorders
- Clusterin in disease pathology
- Dysphagia Assessment and Management
- Cancer-related Molecular Pathways
- Fibroblast Growth Factor Research
- Medical Imaging and Pathology Studies
- Lung Cancer Research Studies
- PARP inhibition in cancer therapy
- Lung Cancer Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- BRCA gene mutations in cancer
- Gastrointestinal Tumor Research and Treatment
University Hospital Heidelberg
2012-2025
Heidelberg University
2013-2025
German Center for Lung Research
2024
München Klinik Schwabing
2016-2023
Olgahospital
2023
Heidelberg University
2019
German Cancer Research Center
2018
RWTH Aachen University
2016
National Cancer Institute
2011
Memorial Sloan Kettering Cancer Center
2011
The identification of gene fusions from RNA sequencing data is a routine task in cancer research and precision oncology. However, despite the availability many computational tools, fusion detection remains challenging. Existing methods suffer poor prediction accuracy are computationally demanding. We developed Arriba, novel algorithm with high sensitivity short runtime. When applied to large collection published pancreatic samples ( n = 803), Arriba identified variety driver fusions, which...
Abstract The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the profiles and outcomes 1,310 patients (rare cancers, 75.5%) enrolled a prospective observational study by German Cancer Consortium that applies whole-genome/exome RNA sequencing to inform care adults with incurable cancers. On basis 472 single six composite biomarkers, cross-institutional tumor board provided evidence-based management recommendations, including diagnostic...
To identify new tumor-suppressor gene candidates relevant for human hepatocarcinogenesis, we performed genome-wide methylation profiling and vertical integration with array-based comparative genomic hybridization (aCGH), as well expression data from a cohort of well-characterized hepatocellular carcinomas (HCCs). Bisulfite-converted DNAs 63 HCCs 10 healthy control livers were analyzed the status more than 14,000 genes. After defining differentially methylated genes in HCCs, integrated their...
Tumor mutational burden (TMB) represents a new determinant of clinical benefit from immune checkpoint blockade that identifies responders independent PD‐L1 expression levels and is currently being explored in trials. Although TMB can be measured directly by comprehensive genomic approaches such as whole‐genome exome sequencing, broad availability, short turnaround times, costs amenability to formalin‐fixed paraffin‐embedded tissue support the use gene panel sequencing for approximating...
Next‐generation sequencing has become a cornerstone of therapy guidance in cancer precision medicine and an indispensable research tool translational oncology. Its rapidly increasing use during the last decade expanded options for targeted tumor therapies, molecular boards have grown accordingly. However, with detection genetic alterations, their interpretation more complex error‐prone, potentially introducing biases reducing benefits clinical practice. To facilitate interdisciplinary...
Assessment of Tumor Mutational Burden (TMB) for response stratification cancer patients treated with immune checkpoint inhibitors is emerging as a new biomarker. Commonly defined the total number exonic somatic mutations, TMB approximates amount neoantigens that potentially are recognized by system. While whole exome sequencing (WES) an unbiased approach to quantify TMB, implementation in diagnostics hampered tissue availability well time and cost constrains. Conversely, panel-based targeted...
Tyrosine kinase inhibitors currently confer the greatest survival gain for nonsmall cell lung cancer (NSCLC) patients with actionable genetic alterations. Simultaneously, increasing number of targets and compounds poses challenge reliable, broad timely molecular assays identification likely to benefit from novel treatments. Here, we demonstrate feasibility clinical utility comprehensive, NGS‐based profiling routine workup advanced NSCLC based on first 3,000 analyzed in our department....
BackgroundTumor mutational burden (TMB) is an emerging biomarker used to identify patients who are more likely benefit from immuno-oncology therapy. Aside various unsettled technical aspects, biological variables such as tumor cell content and intratumor heterogeneity may play important role in determining TMB.MethodsTMB estimates were determined applying the TruSight Oncology 500 targeted sequencing panel. Spatial temporal was analyzed by multiregion (two six samples) of 24 pulmonary...
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 Cholangiocarcinoma (CCA) is a primary malignancy of the biliary tract with dismal prognosis. Recently, several actionable genetic aberrations were identified significant enrichment in intrahepatic CCA, including FGFR2 gene fusions prevalence 10–15%. Recent clinical data demonstrate that these are druggable second-line setting advanced/metastatic disease and efficacy earlier lines therapy being evaluated ongoing trials. This scenario warrants standardised molecular...
•14.3% of patients with rare cancers and/or younger age onset carried a PGV.•PGVs were highly enriched in certain cancer entities, i.e. wild-type GISTs and leiomyosarcomas.•High PGV yields ATM, BRCA2, or PALB2 entities indicated potentially novel genotype–phenotype associations.•75% PGVs predisposition genes newly diagnosed due to study participation (118/157).•45% all supported molecularly informed therapeutic recommendations benefit 40% patients. BackgroundGermline variant evaluation...
Abstract Background Predictive biomarkers in use for immunotherapy advanced non-small cell lung cancer are of limited sensitivity and specificity. We analysed the potential activating KRAS pathogenic TP53 mutations to provide additional predictive information. Methods The study cohort included 713 consecutive patients with adenocarcinomas, negative actionable genetic alterations. Additionally, two previously published surgical patient cohorts were analyzed. Therapy benefit was stratified by...
Mouse Double Minute homolog 4 (MDM4) gene up-regulation often occurs in human hepatocellular carcinoma (HCC), but the molecular mechanisms responsible for its induction remain poorly understood. Here we investigated role of phosphoinositide-3-kinase/v-akt murine thymoma viral oncogene homolog/mammalian target rapamycin (PI3K/AKT/mTOR) axis regulation MDM4 levels HCC. The activity and PI3K/AKT/mTOR pathway was modulated HCC cell lines by way silencing overexpression experiments. Expression...
A growing number of druggable targets and national initiatives for precision oncology necessitate broad genomic profiling many cancer patients. Whole exome sequencing (WES) offers unbiased analysis the entire coding sequence, segmentation-based detection copy alterations (CNAs), accurate determination complex biomarkers including tumor mutational burden (TMB), homologous recombination repair deficiency (HRD), microsatellite instability (MSI). To assess inter-institution variability clinical...
Background The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. organisation immune tumour microenvironment (TME) is expected govern outcomes but spatial immunotypes defined. Objective We hypothesised that deconvolution network architectures could identify clinically relevant HCC. Design conducted highly multiplexed imaging mass cytometry on HCC tissues from 101 patients. performed in-depth single-cell analysis a discovery...
Objective A detailed understanding of the molecular alterations in different forms cholangiocarcinogenesis is crucial for a better cholangiocarcinoma (CCA) and may pave way to early diagnosis treatment options. Design We analysed clinicopathologically well-characterised patient cohort (n=54) with high-grade intraductal papillary (IPNB) or tubulopapillary (ITPN) neoplastic precursor lesions biliary tract correlated results an independent non-IPNB/ITPN associated CCA (n=294). The triplet...
Analysis of selected cancer genes has become an important tool in precision oncology but cannot fully capture the molecular features and, most importantly, vulnerabilities individual tumors. Observational and interventional studies have shown that decision-making based on comprehensive characterization adds significant clinical value. However, complexity heterogeneity resulting data are major challenges for disciplines involved interpretation recommendations individualized care, limited...
Thymic epithelial tumors (TETs) are rare malignancies with limited treatment options and underexplored molecular features. We examined the genomic landscape therapeutic outcomes in 81 patients advanced TETs, including thymic carcinomas (TCs), thymomas, neuroendocrine neoplasms (TNENs), who were enrolled MASTER trial, a prospective observational precision oncology trial. Using whole-genome-sequencing whole-exome-sequencing analysis, transcriptome methylome we identified distinct features...
Oncogenic gene fusions are important drivers in many cancer types, including carcinomas, with diagnostic and therapeutic implications. Hence, sensitive rapid methods for parallel profiling formalin-fixed paraffin-embedded (FFPE) specimens needed. In this study we analyzed a cohort of 517 cases where standard treatment options were exhausted. To end the Archer® DX Solid tumor panel (AMP; 285 cases) Oncomine Comprehensive Assay v3 (OCA; 232 employed. Findings validated by Sanger sequencing,...
Anaplastic lymphoma kinase (ALK) sequencing can identify resistance mechanisms and guide next-line therapy in ALK+ non-small-cell lung cancer (NSCLC), but the clinical significance of other rebiopsy findings remains unclear. We analysed all stage-IV NSCLC patients with longitudinally assessable TP53 status treated our institutions (n = 62). Patients mutations at baseline (TP53mutbas, n 23) had worse overall survival (OS) than initially wild-type tumours (TP53wtbas, 39, 44 vs. 62 months...
Objective We aimed at the identification of genetic alterations that may functionally substitute for CTNNB1 mutation in ß-catenin-activated hepatocellular adenomas (HCAs) and carcinoma (HCC). Design Large cohorts HCA (n=185) HCC (n=468) were classified using immunohistochemistry. The mutational status gene was determined (b-HCA) with least moderate nuclear accumulation. Ultra-deep sequencing used to characterise wild-type HCC. Expression profiling subtypes performed. Results A roof...
Targeted therapies have improved survival and quality of life for patients with non-small-cell lung cancer actionable driver mutations. However, epidermal growth factor receptor (EGFR) human 2 gene (HER2, also known as ERBB2) exon 20 insertions (Ex20mut) are characterized by a poor response to currently approved tyrosine kinase inhibitors immunotherapies. The underlying immune biology is not well understood.We carried out messenger RNA expression profiling adenocarcinomas (ADCs) ERBB2 (n =...