Molecular analysis of clonal evolution of epigenetic and genetic changes in t(14;18) positive follicular lymphoma

Follikuläre Lymphome (FL) sind die zweithäufigsten B-Zell-Lymphome in der westlichen Welt. Charakteristisch für FL ist die Translokation t(14;18), von der angenommen wird, dass sie bereits in der frühen Phase der B-Zell-Entwicklung im Knochenmark entsteht. Diese Translokation findet man nicht nur bei Lymphomen, sie ist auch bei ca. 25% gesunder Individuen nachweisbar. Die genauen Mechanismen der Tumorevolution bei FL sind noch weitgehend unbekannt. Das Ziel dieser Arbeit war die Charakterisierung epigenetischer und genetischer Veränderungen, sowie die Bestimmung phylogentischer Beziehungen zwischen Initial- und Rezidivtumoren in der Evolution t(14;18) positiver FL.Follicular lymphoma (FL) is the second most common B-cell-lymphoma in the western countries. A characteristic hallmark of FL is the translocation t(14;18), suppose to occure at an early B-cell developmental stage in the bone marrow. This translocation is not unique to lymphoma but is also seen in up to 25% of healthy individuals. The exact mechanisms leading to tumour progression in FL are still largely unknown. Therefor the aim of this study was to characterise epigenetic and genetic changes and to identify the phylogenetic relationships between initial and relapse tumour sampples in the progress of evolution of t(14;18) positive FL

Conflicting results of prenatal FISH with different probes for Down's Syndrome critical regions associated with mosaicism for a de novo del(21)(q22) characterised by molecular karyotyping: Case report

For the rapid detection of common aneuploidies either PCR or Fluorescence in situ hybridisation (FISH) on uncultured amniotic fluid cells are widely used. There are different commercial suppliers providing FISH assays for the detection of trisomies affecting the Down's syndrome critical regions (DSCR) in 21q22. We present a case in which rapid FISH screening with different commercial probes for the DSCR yielded conflicting results. Chromosome analysis revealed a deletion of one chromosome 21 in q22 which explained the findings. Prenatally an additional small supernumerary marker chromosome (sSMC) was discovered as well, which could not be characterised. Postnatal chromosome analysis in lymphocytes of the infant revealed complex mosaicism with four cell lines. By arrayCGH the sSMC was provisionally described as derivative chromosome 21 which was confirmed by targeted FISH experiments

Multiplex ligation-dependent probe amplification analysis of the NR0B1(DAX1) locus enables explanation of phenotypic differences in patients with X-linked congenital adrenal hypoplasia

BACKGROUND/AIM:X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency and hypogonadic hypogonadism. It is caused by deletions or point mutations of the NR0B1 gene, on Xp21. AHC can be associated with glycerol kinase deficiency, Duchenne muscular dystrophy and mental retardation (MR), as part of a contiguous gene deletion syndrome. A synthetic probe set for multiplex ligation-dependent probe amplification analysis was developed to confirm and characterize NR0B1 deletions in patients with AHC and to correlate their genotypes with their divergent phenotypes. RESULTS:In 2 patients, isolated AHC was confirmed, while a patient at risk for metabolic crisis was revealed as the deletion extends to the GK gene. A deletion extending to IL1RAPL1 was confirmed in both patients showing MR. Thus, a good genotype-phenotype correlation was confirmed. CONCLUSIONS:Multiplex ligation-dependent probe amplification analysis is a valuable tool to detect NR0B1 and contiguous gene deletions in patients with AHC. It is especially helpful for IL1RAPL1 deletion detection as no clinical markers for MR are available. Furthermore, multiplex ligation-dependent probe amplification has the advantage to identify female carriers that, depending on the deletion extension, have a high risk of giving birth to children with MR, AHC, glycerol kinase deficiency and Duchenne muscular dystrophy

Genomic basis of a social polymorphism in a halictid bee

Item does not contain fulltex

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing

Pipeline for Large-Scale Microdroplet Bisulfite PCR-Based Sequencing Allows the Tracking of Hepitype Evolution in Tumors

Cytosine methylation provides an epigenetic level of cellular plasticity that is important for development, differentiation and cancerogenesis. We adopted microdroplet PCR to bisulfite treated target DNA in combination with second generation sequencing to simultaneously assess DNA sequence and methylation. We show measurement of methylation status in a wide range of target sequences (total 34 kb) with an average coverage of 95% (median 100%) and good correlation to the opposite strand (rho = 0.96) and to pyrosequencing (rho = 0.87). Data from lymphoma and colorectal cancer samples for SNRPN (imprinted gene), FGF6 (demethylated in the cancer samples) and HS3ST2 (methylated in the cancer samples) serve as a proof of principle showing the integration of SNP data and phased DNA-methylation information into “hepitypes” and thus the analysis of DNA methylation phylogeny in the somatic evolution of cancer

Atlas der Stadt- und Regionalentwicklung 2022: Unter besonderer Berücksichtigung der räumlichen Auswirkungen von COVID-19

Der Ausbruch der COVID-19-Pandemie im Jahr 2020 hat massive Einschnitte für Gesellschaft und Wirtschaft nach sich gezogen. Kontaktbeschränkungen, Schulschließungen, Homeoffice und Maskenpflicht veränderten den Alltag aller Menschen. Die Pandemie hat Gewissheiten in Frage gestellt, aber auch den Blick auf Herausforderungen in Gesellschaft, Wirtschaft und Verwaltung geschärft. Sie hat den Weg geöffnet für neue Formen der mobilen Arbeit. Sie hat Debatten um soziale Ungleichheit und unterschiedliche Bildungschancen befeuert. Die Pandemie hat gezeigt, wie staatliche Instrumente wie das Kurzarbeitergeld die Arbeitsmärkte wirksam gestützt haben. Sie hat den Blick auf die Zukunft der Innenstädte gelenkt und Impulse für die Verkehrswende gesetzt. Und sie hat deutlich gemacht, dass die Digitalisierung in allen Bereichen noch schneller vorangehen muss als bisher. Der vorliegende Atlas umreißt in Karten und Abbildungen die Entwicklungen in den Teilräumen Deutschlands und über Daten erfassbare Veränderungen zwischen 2020, dem ersten Pandemiejahr, und 2019. In Teilbereichen liegen auch schon kleinräumige Informationen für das zweite Pandemiejahr 2021 vor. Welche Veränderungen sind bereits kurzfristig zur "vorpandemischen Normalität" beobachtbar? Lassen sich die vermuteten Veränderungen überhaupt in den Kennzahlen und Entwicklungsverläufen der Regionen ablesen? Wie groß sind die regionalen Unterschiede hinsichtlich u.a. der demografischen, sozialen, Siedlungsstruktur; welche werden durch die Pandemie verstärkt? Die datengestützten Einschätzungen zum COVID-19-Effekt auf die regionalen Entwicklungen wird über Forschungsergebnisse und Literatur untermauert. In vielen Fällen wirkt sich die Pandemie beschleunigend auf Entwicklungen, die sich bereits vor der Pandemie abzeichneten