Reinhold Schäfer

Reinhold Schäfer
Charité Universitätsmedizin Berlin | Charité · Institute of Pathology

Prof. Dr. rer. nat.

About

244
Publications
12,124
Reads
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6,096
Citations
Additional affiliations
April 1996 - present
Charité Universitätsmedizin Berlin
Position
  • Professor of Molecular Tumor Pathology
April 1988 - March 1996
University Hospital Zürich
Position
  • Head, Division of Cancer Research/Leiter der Abteilung Krebsforschung
May 1985 - April 1988
Ludwig Institute for Cancer Research Australia
Position
  • Group Leader
Education
May 1976 - January 1978
Max Planck Institute for Experimental Medicine
Field of study
  • Molecular Genetics, postdoctoral fellow
October 1972 - April 1976
University of Bonn
Field of study
  • Biology

Publications

Publications (244)
Article
Background Targeted therapies for metastatic uveal melanoma have shown limited benefit in biomarker-unselected populations. The Treat20 Plus study prospectively evaluated the feasibility of a precision oncology strategy in routine clinical practice. Patients and methods Fresh biopsies were analyzed by high-throughput genomics (whole-genome, whole-...
Article
Full-text available
Recent evidence demonstrates that colon cancer stem cells (CSCs) can generate neurons that synapse with tumor innervating fibers required for tumorigenesis and disease progression. Greater understanding of the mechanisms that regulate CSC driven tumor neurogenesis may therefore lead to more effective treatments. RNA-sequencing analyses of ALDHPosit...
Article
The COSMIC database (version 94) lists 576 genes in the Cancer Gene Census which have a defined function as drivers of malignancy (oncogenes) or as tumour suppressors (Tier 1). In addition, there are 147 genes with similar functions, but which are less well characterised (Tier 2). Furthermore, the overall number of genetic alterations found in tumo...
Article
Full-text available
Recent data suggests that therapy resistant quiescent cancer stem cells (qCSCs) are the source of relapse in colon cancer. Here, using colon cancer patient-derived organoids (PDOs) and xenografts (PDXs), we identify rare long-term label-retaining qCSCs that can re-enter the cell cycle to generate new tumors. RNA-sequencing analyses demonstrated tha...
Article
In colorectal cancer (CRC), the prevalence of NRAS mutations (5–9%) is inferior to that of KRAS mutations (40–50%). NRAS mutations feature lately during tumour progression and drive resistance to anti-EGFR therapy in KRAS wild-type tumours. To elucidate specific functions of NRAS mutations in CRC, we expressed doxycycline-inducible G12D and Q61K mu...
Article
Full-text available
Oncoproteins such as the BRAFV600E kinase endow cancer cells with malignant properties, but they also create unique vulnerabilities. Targeting of BRAFV600E-driven cytoplasmic signaling networks has proved ineffective, as patients regularly relapse with reactivation of the targeted pathways. We identify the nuclear protein SFPQ to be synthetically l...
Article
Full-text available
To unravel vulnerabilities of KRAS-mutant CRC cells, a shRNA-based screen specifically inhibiting MAPK pathway components and targets was performed in CaCo2 cells harboring conditional oncogenic KRASG12V. The custom-designed shRNA library comprised 121 selected genes, which were previously identified to be strongly regulated in response to MEK inhi...
Article
Background: Reliable and reproducible interpretation of molecular aberrations constitutes a bottleneck of precision medicine. Evidence-based decision management systems may improve rational therapy recommendations. To cope with an increasing amount of complex molecular data in the clinical care of patients with cancer, we established a workflow fo...
Article
Full-text available
Background: Diagnosis and treatment decisions in cancer increasingly depend on a detailed analysis of the mutational status of a patient's genome. This analysis relies on previously published information regarding the association of variations to disease progression and possible interventions. Clinicians to a large degree use biomedical search eng...
Conference Paper
Mutations in the transforming growth factor-β (TGF-β) pathway occur frequently in colorectal cancers (CRC). TGF-β is integral for key cellular processes, including proliferation, migration, differentiation and apoptosis. TGF-β/SMAD4 controls the activation of the pathway. A previously described R361H mutation in SMAD4 has been correlated with decre...
Article
PURPOSE Precision oncology depends on the availability of up-to-date, comprehensive, and accurate information about associations between genetic variants and therapeutic options. Recently, a number of knowledge bases (KBs) have been developed that gather such information on the basis of expert curation of the scientific literature. We performed a q...
Article
e13033 Background: Panel sequencing (PS) has become a standard-of-care in cancer diagnostics. More comprehensive analyses such as whole-exome (WES) or RNA sequencing (RNAseq) allow for the detection of rare and unknown genetic aberrations that are not covered by predefined assays. The clinical impact of targeted versus comprehensive genomic assays...
Article
Commonly occurring genetic alterations and patient-specific genetic features are increasingly used to predict the possible action of targeted cancer therapies. Although several lines of evidence have suggested that preclinical and clinical responses concur, the heterogeneity of tumors remains a severe obstacle in routinely translating preclinical d...
Preprint
Full-text available
Organoid cultures derived from colorectal cancer (CRC) samples are increasingly used as preclinical models for studying tumor biology and the effects of targeted therapies under conditions capturing in vitro the genetic make-up of heterogeneous and even individual neoplasms. While 3D cultures are initiated from surgical specimens comprising multipl...
Conference Paper
Full-text available
Diagnosis and treatment decisions in cancer increasingly depend on a detailed analysis of the mutational status of a patient's genome. This analysis relies on previously published information regarding the association of variations to disease progression and possible interventions. Clinicians to a large degree use biomedical search engines to obtai...
Article
Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR‐targeted therapies in colorectal cancer. Gene‐body methylation sites, which show a strong inverse correlation with AREG and EREG gene expression, were identified in cell lines using targeted 454 FLX‐bisulfite...
Article
Full-text available
Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs). To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched...
Chapter
For decades of molecular cancer research, immortal cancer cell lines have served as an easily accessible source for basic cancer biology research and preclinical testing of anticancer drugs. However, numerous studies have suggested that these cell lines poorly recapitulate the diversity, heterogeneity, and resulting drug resistance or relapse in pa...
Data
Several lines of evidence have suggested that stemness and acquired resistance to targeted inhibitors or chemotherapeutics are mechanistically linked. Here we observed high cell surface and total levels of nerve growth factor receptor/CD271, a marker of melanoma-initiating cells, in sub-populations of chemoresistant cell lines. CD271 expression was...
Article
Full-text available
Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I–IV) and developed a pre-clinical platform generating...
Data
Comparison of mutations between 5 PDX derived from 150_MET2.
Data
Assignment of OT samples to molecular groups.
Data
Functional annotation of the OT_NMF and OT_C clusters.
Data
Gene signatures related to drug sensitivity in patient derived models.
Data
Classification of responders and non-responders for 5-FU treatment.
Data
Combined list of alterations in the OT cohort.
Data
Discordant SNVs and indels in matched patient and model pairs.
Data
Expression values of differentially expressed genes in 151_MET_CELL1 Wnt -negative, -low, -high sorted fractions and unsorted cells.
Data
Classification of responders and non-responders for cetuximab treatment.
Data
Copy Number Variations (CNVs) in the OT cohort.
Data
Gene signatures used for the classification of OT primary tumour samples and models.
Data
Values of mean pattern matrices and enrichment scores (ES) of single sample gene set enrichment analysis (ssGSEA).
Data
List of identified gene fusions in the OT cohort.
Article
Full-text available
Genetic heterogeneity between and within tumours is a major factor determining cancer progression and therapy response. Here we examined DNA sequence and DNA copy-number heterogeneity in colorectal cancer (CRC) by targeted high-depth sequencing of 100 most frequently altered genes. In 97 samples, with primary tumours and matched metastases from 27...
Data
List of SNVs and their allele frequency from the inter-tumor heterogeneity study. The SNVs shown here are post filtering of: non-synonymous and intronic SNVs, Sanger and SNuPE non-validated SNVs, and patient normal-tissue single nucleotide polymorphisms. A cut-off for quality of Q=50 was used. SNVs found in large repeat areas were also removed.
Data
SNVs after filtering out non-synonymous and intronic SNVs, Sanger and SNuPE non-validated SNVs and single nucleotide polymorphisms found in the healthy normal-tissue (3.1-1). A cut-off for quality of Q=50 was used.
Data
3D reconstruction of a stage II colon cancer rotating 360° around the horizontal axis and color coded by DNA copy number variation (CNV). Two main clusters are shown in green and violet. Red, blue and green axis key (left) indicates the x, y and z axis respectively. Z axis denominates the proximal - distal axis along the colon lumen. Distinct compa...
Data
This application is only compatible with windows operating system. Prerequisites: Windows 7/8/10 with .net 4.5 and Direct X. First unzip the file. To install XNA run XNA Framework 4.0 Redist.msi . Next run "start3D.bat". The mesh visualization will open in a new window. Following inputs are possible while the program is running: "1", "2", "3", "4"...
Article
Full-text available
Several lines of evidence have suggested that stemness and acquired resistance to targeted inhibitors or chemotherapeutics are mechanistically linked. Here we observed high cell surface and total levels of nerve growth factor receptor/CD271, a marker of melanoma-initiating cells, in sub-populations of chemoresistant cell lines. CD271 expression was...