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17 Publications matching the given criteria: (Clear all filters)
Author: Hans Binder17
DNA methylation, transcriptome and genetic copy number signatures of diffuse cerebral WHO grade II/III gliomas resolve cancer heterogeneity and development.
GGN - German Glioma Network

Abstract (Expand)

BACKGROUND: Diffuse lower WHO grade II and III gliomas (LGG) are slowly progressing brain tumors, many of which eventually transform into a more aggressive type. LGG is characterized by widespread … genetic and transcriptional heterogeneity, yet little is known about the heterogeneity of the DNA methylome, its function in tumor biology, coupling with the transcriptome and tumor microenvironment and its possible impact for tumor development. METHODS: We here present novel DNA methylation data of an LGG-cohort collected in the German Glioma Network containing about 85% isocitrate dehydrogenase (IDH) mutated tumors and performed a combined bioinformatics analysis using patient-matched genome and transcriptome data. RESULTS: Stratification of LGG based on gene expression and DNA-methylation provided four consensus subtypes. We characterized them in terms of genetic alterations, functional context, cellular composition, tumor microenvironment and their possible impact for treatment resistance and prognosis. Glioma with astrocytoma-resembling phenotypes constitute the largest fraction of nearly 60%. They revealed largest diversity and were divided into four expression and three methylation groups which only partly match each other thus reflecting largely decoupled expression and methylation patterns. We identified a novel G-protein coupled receptor and a cancer-related 'keratinization' methylation signature in in addition to the glioma-CpG island methylator phenotype (G-CIMP) signature. These different signatures overlap and combine in various ways giving rise to diverse methylation and expression patterns that shape the glioma phenotypes. The decrease of global methylation in astrocytoma-like LGG associates with higher WHO grade, age at diagnosis and inferior prognosis. We found analogies between astrocytoma-like LGG with grade IV IDH-wild type tumors regarding possible worsening of treatment resistance along a proneural-to-mesenchymal axis. Using gene signature-based inference we elucidated the impact of cellular composition of the tumors including immune cell bystanders such as macrophages. CONCLUSIONS: Genomic, epigenomic and transcriptomic factors act in concert but partly also in a decoupled fashion what underpins the need for integrative, multidimensional stratification of LGG by combining these data on gene and cellular levels to delineate mechanisms of gene (de-)regulation and to enable better patient stratification and individualization of treatment.

Authors: H. Binder, E. Willscher, H. Loeffler-Wirth, L. Hopp, D. T. W. Jones, S. M. Pfister, M. Kreuz, D. Gramatzki, E. Fortenbacher, B. Hentschel, M. Tatagiba, U. Herrlinger, H. Vatter, J. Matschke, M. Westphal, D. Krex, G. Schackert, J. C. Tonn, U. Schlegel, H. J. Steiger, W. Wick, R. G. Weber, M. Weller, M. Loeffler

Date Published: 25th Apr 2019

Publication Type: Not specified

Human Diseases: brain glioma

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma.
MMML - Molecular mechanisms in malignant lymphoma

Abstract (Expand)

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.

Authors: C. Lopez, K. Kleinheinz, S. M. Aukema, M. Rohde, S. H. Bernhart, D. Hubschmann, R. Wagener, U. H. Toprak, F. Raimondi, M. Kreuz, S. M. Waszak, Z. Huang, L. Sieverling, N. Paramasivam, J. Seufert, S. Sungalee, R. B. Russell, J. Bausinger, H. Kretzmer, O. Ammerpohl, A. K. Bergmann, H. Binder, A. Borkhardt, B. Brors, A. Claviez, G. Doose, L. Feuerbach, A. Haake, M. L. Hansmann, J. Hoell, M. Hummel, J. O. Korbel, C. Lawerenz, D. Lenze, B. Radlwimmer, J. Richter, P. Rosenstiel, A. Rosenwald, M. B. Schilhabel, H. Stein, S. Stilgenbauer, P. F. Stadler, M. Szczepanowski, M. A. Weniger, M. Zapatka, R. Eils, P. Lichter, M. Loeffler, P. Moller, L. Trumper, W. Klapper, S. Hoffmann, R. Kuppers, B. Burkhardt, M. Schlesner, R. Siebert

Date Published: 29th Mar 2019

Publication Type: Not specified

Human Diseases: lymphoma, Burkitt lymphoma

Longitudinal anthropometry of children and adolescents using 3D-body scanning.
LIFE - Leipzig Research Center for Civilization Diseases, LIFE Child

Abstract (Expand)

3D-body scanning anthropometry is a suitable method for characterization of physiological development of children and adolescents, and for understanding onset and progression of disorders like overweight … and obesity. Here we present a novel body typing approach to describe and to interpret longitudinal 3D-body scanning data of more than 800 children and adolescents measured in up to four follow-ups in intervals of 1 year, referring to an age range between 6 and 18 years. We analyzed transitions between body types assigned to lower-, normal- and overweight participants upon development of children and adolescents. We found a virtually parallel development of the body types with only a few transitions between them. Body types of children and adolescents tend to conserve their weight category. 3D body scanning anthropometry in combination with body typing constitutes a novel option to investigate onset and progression of obesity in children.

Authors: H. Loeffler-Wirth, M. Vogel, T. Kirsten, F. Glock, T. Poulain, A. Korner, M. Loeffler, W. Kiess, H. Binder

Date Published: 14th Sep 2018

Publication Type: Not specified

Human Diseases: obesity

Body typing of children and adolescents using 3D-body scanning.
LIFE Child

Abstract (Expand)

Three-dimensional (3D-) body scanning of children and adolescents allows the detailed study of physiological development in terms of anthropometrical alterations which potentially provide early onset … markers for obesity. Here, we present a systematic analysis of body scanning data of 2,700 urban children and adolescents in the age range between 5 and 18 years with the special aim to stratify the participants into distinct body shape types and to describe their change upon development. In a first step, we extracted a set of eight representative meta-measures from the data. Each of them collects a related group of anthropometrical features and changes specifically upon aging. In a second step we defined seven body types by clustering the meta-measures of all participants. These body types describe the body shapes in terms of three weight (lower, normal and overweight) and three age (young, medium and older) categories. For younger children (age of 5-10 years) we found a common 'early childhood body shape' which splits into three weight-dependent types for older children, with one or two years delay for boys. Our study shows that the concept of body types provides a reliable option for the anthropometric characterization of developing and aging populations.

Authors: H. Loeffler-Wirth, M. Vogel, T. Kirsten, F. Glock, T. Poulain, A. Korner, M. Loeffler, W. Kiess, H. Binder

Date Published: 21st Oct 2017

Publication Type: Not specified

Human Diseases: obesity

Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome.
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Colorectal cancer (CRC) arising in Lynch syndrome (LS) comprises tumours with constitutional mutations in DNA mismatch repair genes. There is still a lack of whole-genome and transcriptome studies of … LS-CRC to address questions about similarities and differences in mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC, and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch repair in LS colonic mucosa and the possible role of immune editing. Here, we provide a first molecular characterization of LS tumours and of matched tumour-distant reference colonic mucosa based on whole-genome DNA-sequencing and RNA-sequencing analyses. Our data support two subgroups of LS-CRCs, G1 and G2, whereby G1 tumours show a higher number of somatic mutations, a higher amount of microsatellite slippage, and a different mutation spectrum. The gene expression phenotypes support this difference. Reference mucosa of G1 shows a strong immune response associated with the expression of HLA and immune checkpoint genes and the invasion of CD4+ T cells. Such an immune response is not observed in LS tumours, G2 reference and normal (non-Lynch) mucosa, and sporadic CRC. We hypothesize that G1 tumours are edited for escape from a highly immunogenic microenvironment via loss of HLA presentation and T-cell exhaustion. In contrast, G2 tumours seem to develop in a less immunogenic microenvironment where tumour-promoting inflammation parallels tumourigenesis. Larger studies on non-neoplastic mucosa tissue of mutation carriers are required to better understand the early phases of emerging tumours. Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Authors: H. Binder, L. Hopp, M. R. Schweiger, S. Hoffmann, F. Juhling, M. Kerick, B. Timmermann, S. Siebert, C. Grimm, L. Nersisyan, A. Arakelyan, M. Herberg, P. Buske, H. Loeffler-Wirth, M. Rosolowski, C. Engel, J. Przybilla, M. Peifer, N. Friedrichs, G. Moeslein, M. Odenthal, M. Hussong, S. Peters, S. Holzapfel, J. Nattermann, R. Hueneburg, W. Schmiegel, B. Royer-Pokora, S. Aretz, M. Kloth, M. Kloor, R. Buettner, J. Galle, M. Loeffler

Date Published: 21st Jul 2017

Publication Type: Not specified

Human Diseases: Lynch syndrome, colorectal cancer

Novel Anthropometry Based on 3D-Bodyscans Applied to a Large Population Based Cohort.
LIFE Adult, Genetical Statistics and Systems Biology

Abstract (Expand)

Three-dimensional (3D) whole body scanners are increasingly used as precise measuring tools for the rapid quantification of anthropometric measures in epidemiological studies. We analyzed 3D whole body … scanning data of nearly 10,000 participants of a cohort collected from the adult population of Leipzig, one of the largest cities in Eastern Germany. We present a novel approach for the systematic analysis of this data which aims at identifying distinguishable clusters of body shapes called body types. In the first step, our method aggregates body measures provided by the scanner into meta-measures, each representing one relevant dimension of the body shape. In a next step, we stratified the cohort into body types and assessed their stability and dependence on the size of the underlying cohort. Using self-organizing maps (SOM) we identified thirteen robust meta-measures and fifteen body types comprising between 1 and 18 percent of the total cohort size. Thirteen of them are virtually gender specific (six for women and seven for men) and thus reflect most abundant body shapes of women and men. Two body types include both women and men, and describe androgynous body shapes that lack typical gender specific features. The body types disentangle a large variability of body shapes enabling distinctions which go beyond the traditional indices such as body mass index, the waist-to-height ratio, the waist-to-hip ratio and the mortality-hazard ABSI-index. In a next step, we will link the identified body types with disease predispositions to study how size and shape of the human body impact health and disease.

Authors: H. Loffler-Wirth, E. Willscher, P. Ahnert, K. Wirkner, C. Engel, M. Loeffler, H. Binder

Date Published: 29th Jul 2016

Publication Type: Not specified

Human Diseases: obesity

The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany.
LIFE Adult, Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 … inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. METHODS/DESIGN: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. DISCUSSION: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

Authors: M. Loeffler, C. Engel, P. Ahnert, D. Alfermann, K. Arelin, R. Baber, F. Beutner, H. Binder, E. Brahler, R. Burkhardt, U. Ceglarek, C. Enzenbach, M. Fuchs, H. Glaesmer, F. Girlich, A. Hagendorff, M. Hantzsch, U. Hegerl, S. Henger, T. Hensch, A. Hinz, V. Holzendorf, D. Husser, A. Kersting, A. Kiel, T. Kirsten, J. Kratzsch, K. Krohn, T. Luck, S. Melzer, J. Netto, M. Nuchter, M. Raschpichler, F. G. Rauscher, S. G. Riedel-Heller, C. Sander, M. Scholz, P. Schonknecht, M. L. Schroeter, J. C. Simon, R. Speer, J. Staker, R. Stein, Y. Stobel-Richter, M. Stumvoll, A. Tarnok, A. Teren, D. Teupser, F. S. Then, A. Tonjes, R. Treudler, A. Villringer, A. Weissgerber, P. Wiedemann, S. Zachariae, K. Wirkner, J. Thiery

Date Published: 22nd Jul 2015

Publication Type: Not specified

Human Diseases: disease of mental health, mental depression, vascular disease, allergic hypersensitivity disease, sleep disorder, retinal degeneration

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