PubMed | Zentrum fur Humangenetik, MVZ genteQ, U.S. National Cancer Institute, Mitteldeutscher Praxisverbund Humangenetik and 23 more.
Type: Journal Article | Journal: British journal of cancer | Year: 2015
Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These RASopathies also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown.We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry.We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR)=10.5, 95% confidence interval=5.4-18.3). The specific cancers included juvenile myelomonocytic leukaemia=4; brain tumour=3; acute lymphoblastic leukaemia=2; rhabdomyosarcoma=2; and neuroblastoma=1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4.These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours.
Geisthovel F.,Centrum fur Gynakologische Endokrinologie und Reproduktionsmedizin Freiburg CERF |
Ochsner A.,Centrum fur Gynakologische Endokrinologie und Reproduktionsmedizin Freiburg CERF |
Wetzka B.,Centrum fur Gynakologische Endokrinologie und Reproduktionsmedizin Freiburg CERF |
Klein H.-G.,Zentrum For Humangenetik Und Laboratoriumsdiagnostik Mvz |
Frommel M.,University of Kiel
Gynakologische Endokrinologie | Year: 2015
Aging of human ovaries is evolutionarily determined and includes both a quantitative decrease of the follicle-oocyte pool and a concomitant increase of aneuploid oocytes leading to an increased incidence of trisomy 21 in women ≥ 35 years of age. Ovarian aneuploidy is caused mainly by functional and structural defects of the mechanisms related to the segregation of chromosomes in meiosis I of the ageing oocyte. Non-invasive prenatal testing (NIPT), meaning the detection of fetal chromosomal material in maternal blood by DNA sequence analysis, has been established for the screening of fetal aneuploidies from the 9th week of pregnancy onwards. The NIPT is a simple somatic test which helps to avoid invasive prenatal diagnostic procedures. From the perspective of reproductive medicine there are several indications for NIPT, particularly in pregnancies resulting from artificial reproductive technologies (ART). In general NIPT is indicated in women ≥ 35 years undergoing infertility treatment (also for multiple pregnancies) or social freezing and embryo donation from a mother > 35 years. Additional indications might be pregnancies resulting from ART combined with polar body biopsy for genetic screening because of maternal age or maternal translocation or with preimplantation genetic diagnoses in cases of paternal translocation. However, so far there is no NIPT procedure specifically for detecting translocations available. A couple should receive pretherapeutic counseling on the NITP and its indications and this test should be offered to pregnant women only after genetic counseling. In Germany, a mother can freely decide to interrupt a pregnancy before the 12th week of pregnancy but thereafter needs a medical assessment. © 2015, Springer-Verlag Berlin Heidelberg.
Busse B.,Zentrum For Humangenetik Und Laboratoriumsdiagnostik Mvz |
Tepedino M.-F.,Zentrum For Humangenetik Und Laboratoriumsdiagnostik Mvz |
Rupprecht W.,Zentrum For Humangenetik Und Laboratoriumsdiagnostik Mvz |
Klein H.-G.,Zentrum For Humangenetik Und Laboratoriumsdiagnostik Mvz
LaboratoriumsMedizin | Year: 2015
Hemoglobinopathies belong to the most common monogenic hereditary diseases worldwide. A particularly high prevalence is seen in the Mediterranean countries, in parts of Asia, the Middle East and West Africa. Nevertheless, due to migration hemoglobinopathies play an increasingly important role in Germany as well. Basic testing consists of blood count and hemoglobin differentiation. In addition, an iron deficiency should be excluded if necessary. Molecular genetic testing is used for the verification of hematologic findings and serves in the assessment of risk for a severe form of a hemoglobinopathy in offspring. In order to ensure efficient diagnostics, family history and previous findings of the patient should be communicated to the laboratory. This is especially crucial in the case of prenatal diagnostics. © 2015 by De Gruyter.
Hinrichsen T.,Zentrum For Humangenetik Und Laboratoriumsdiagnostik Mvz |
Dworniczak J.K.,TU Munich |
Wachter O.,Zentrum For Humangenetik Und Laboratoriumsdiagnostik Mvz |
Dworniczak B.,University of Munster |
Dockhorn-Dworniczak B.,Zentrum For Humangenetik Und Laboratoriumsdiagnostik Mvz
LaboratoriumsMedizin | Year: 2016
The term liquid biopsy comprises methods of blood-based analysis of nucleic acids, which are increasingly under discussion in oncology and personalized medicine, and are already applied in individual cases. The analysis of tumor markers, which in certain tumor diseases can be found as protein markers in vast amounts in the blood, constitutes a primary form of liquid biopsy. Cell-free circulating DNA fragments in the blood (ctDNA), which reflect the genetic profile of a tumor cell and are released in different ways by the tumor, represent a new class of more specific and sensitive biomarkers that can be correlated with the dynamics of the tumor disease. New technologies based on PCR and sequencing techniques pave the way for diagnostic approaches to define molecular tumor characteristics, not only in tumor tissue but also in the blood, by analyzing cell-free circulating DNA. The combination of molecular profiling of the tumor with ctDNA analytics by liquid biopsy is a promising step in the advancement of precision medicine. © 2016 Walter de Gruyter GmbH, Berlin/Boston.
Klein H.-G.,Zentrum For Humangenetik Und Laboratoriumsdiagnostik Mvz |
Rost I.,Zentrum For Humangenetik Und Laboratoriumsdiagnostik Mvz
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz | Year: 2015
Modern genetic analysis methods such as DNA arrays (gene chips) or high-throughput DNA sequencing of the next generation (Next Generation Sequencing, NGS) have once again accelerated the pace of innovation that has been powered by genome research over the past 10 years of the “post-genomic era”. The present paper introduces array and NGS methods as two important innovation driving methods and provides examples for their application in large-scale scientific projects. However, a broad application of these very powerful technologies for genetic screening for the purpose of disease prevention is currently not yet in sight. The complexity of the interaction of genes, gene products and the environment has so far exceeded all expectations, suggesting that reliable statements about the medical relevance of common genetic variants can presently only be made in a few areas such as pharmacogenetics and oncology. We also discuss ethical issues raised by genetic population screening. The aim of this paper is to provide a brief outline of the development of methods in molecular genetics to the now dominant modern technologies and present their applications in research, in the diagnosis of rare diseases, and in terms of screening approaches. © 2014, Springer-Verlag Berlin Heidelberg.