A5082045541- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Biochemical Analysis and Sensing Techniques
- Lung Cancer Research Studies
- Genetic factors in colorectal cancer
- Regulation of Appetite and Obesity
- Cancer Immunotherapy and Biomarkers
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Colorectal Cancer Treatments and Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- PARP inhibition in cancer therapy
- Nutrition, Genetics, and Disease
- Renal cell carcinoma treatment
- Epigenetics and DNA Methylation
- Pancreatic and Hepatic Oncology Research
- Cancer-related molecular mechanisms research
- Eating Disorders and Behaviors
- Cancer Diagnosis and Treatment
- Prostate Cancer Treatment and Research
- Adipose Tissue and Metabolism
- Renal and related cancers
- Bipolar Disorder and Treatment
- Healthcare cost, quality, practices
- Circular RNAs in diseases
University Hospital Heidelberg
2016-2025
Heidelberg University
2016-2025
Bristol-Myers Squibb (Germany)
2023
Pfizer (United Kingdom)
2023
Roche (Switzerland)
2023
Novartis (Ireland)
2023
Seagen (Canada)
2023
AstraZeneca (Brazil)
2023
Illumina (United States)
2023
Eli Lilly (United States)
2023
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...
BackgroundThe efficacy of checkpoint inhibitors for non-small cell lung cancer (NSCLC) with MET exon 14 skipping (METΔ14ex) remains controversial.Materials and methods110 consecutive METΔ14ex NSCLC patients receiving first-line chemotherapy (CHT) and/or immunotherapy (IO) in 10 German centers between 2016-2022 were analyzed.ResultsCombined CHT-IO was given to 35/110 (32%) patients, IO alone 43/110 (39%), CHT 32/110 (29%) upfront. Compared CHT, showed longer progression-free survival (median...
V-domain Ig-containing suppressor of T cell activation (VISTA) is a unique immune checkpoint protein, which was reported to display both receptor and ligand activities. However, the mechanisms regulation VISTA activity functions by factors tumour microenvironment (TME) remain unclear understanding these processes required in order develop successful personalised cancer immunotherapeutic strategies approaches. Here we report for very first time that interacts with another protein galectin-9...
Although heritability of human body weight is assumed to be high, only a small fraction the variance can as yet attributed molecular genetic factors. Single monogenic forms obesity have been identified. Functionally relevant coding mutations in melanocortin-4 receptor gene occur 1–6% extremely obese children and adolescents thus represent most common major effect. Genome-wide association studies (GWAS) had previously identified 14 loci with genome-wide significant (p < 5 x 10–8)...
Abstract Children with attention‐deficit/hyperactivity disorder (ADHD) have a higher rate of obesity than children without ADHD. Obesity risk alleles may overlap those relevant for We examined whether an increased body mass index (BMI) are associated ADHD and related quantitative traits (inattention hyperactivity/impulsivity). screened 32 single nucleotide polymorphisms (SNPs) in genome‐wide association study (GWAS) based on 495 patients 1,300 population‐based controls performed silico...
Abstract The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome‐wide association studies (GWAS) have not led to the identification significant results. We performed a GWAS based on 495 German young patients with ADHD (according DSM‐IV criteria; Human660W‐Quadv1; Illumina, San Diego, CA) and 1,300 population‐based adult controls (HumanHap550v3; Illumina). Some genes neighboring single nucleotide polymorphisms...
Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) may exceed 20%, and BTC is currently the leading cause death patients with PSC. To open new avenues for management, we aimed to delineate clinically relevant genomic pathological features a large panel PSC-associated (PSC-BTC).We analyzed formalin-fixed, paraffin-embedded tumor tissue from 186 PSC-BTC 11 centers eight countries all anatomical locations included. We performed DNA sequencing at 42 genetic loci...
PD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management.We analyzed NSCLC patients receiving from 2012 to 2020 in a German academic center.IrAE showed comparable frequencies stage IV (198/894 or 22%) vs. III (14/45 31%, p = 0.15), after anti-PD-(L)1 monotherapy chemoimmunotherapy (139/483 58/213, 0.75), and across treatment lines. In IV, irAE occurred 3.1 months median, affected...
Objective The melanocortin receptor accessory protein 2 (MRAP2) is relevant for weight regulation in mice and humans. This function likely mediated by of the melanocortin‐4 (MC4R). Functional implications human MRAP2 mutations have not been described yet. Methods A mutation screen was conducted 184 children adolescents with (extreme) obesity lean controls. Detected nonsynonymous variants were genotyped larger independent study groups (300 people 436 individuals normal weight). influence...
Defects in DNA damage repair caused by mutations BRCA1/2, ATM or other genes have been shown to play an important role the development and progression of prostate cancer. The influence such on anti-tumor immunity cancer, however, is largely unknown. To better understand correlation between BRCA1/2 immune phenotype we characterized infiltrate eight BRCA2-mutated tumors comparison with wild-type patients T-cell receptor sequencing immunohistochemistry for CD45, CD4, CD8, FOXP3, CD163. In...
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...