Search

Your search keyword '"Schweiger, M.R."' showing total 9 results
Start Over Author "Schweiger, M.R."
9 results on '"Schweiger, M.R."'

1. Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies

Author

Thomalla, D., Beckmann, L., Grimm, C., Oliverio, M., Meder, L., Herling, C.D., Nieper, P., Feldmann, T., Merkel, O., Lorsy, E., da Palma Guerreiro, A., von Jan, J., Kisis, I., Wasserburger, E., Claasen, J., Faitschuk-Meyer, E., Altmüller, J., Nürnberg, P., Yang, T.-P., Lienhard, M., Herwig, R., Kreuzer, K.-A., Pallasch, C.P., Büttner, R., Schäfer, S.C., Hartley, J., Abken, H., Peifer, M., Kashkar, H., Knittel, G., Eichhorst, B., Ullrich, R.T., Herling, M., Reinhardt, H.C., Hallek, M., Schweiger, M.R., and Frenzel, L.P.

Published
2022
Full Text
View/download PDF

3. Transcriptional signature induced by a C-terminal c-Src mutant in a human breast cell line

Author

Broecker, F., Hardt, C., Herwig, R., Timmermann, B., Kerick, M., Wunderlich, A., Schweiger, M.R., Borsig, L., Heikenwälder, M., Lehrach, H., and Moelling, K.

Subjects
Oncogene, Pdz Domain, C-src, Metastasis, Migration, Transcriptome
Abstract

Deletions at the C-terminus of the proto-oncogene protein c-Src kinase are characteristic of the viral oncogene protein v-Src and are present in some advanced human colon cancers. They are associated with increased kinase activity and elevated cellular invasiveness. Here, we analyzed the mRNA expression signature of a constitutively active C-terminal mutant of c-Src, c-Src(mt), in comparison to its wildtype protein, c-Src(wt), expressed in the human non-transformed breast epithelial cell line MCF-10A. We demonstrated previously that the mutant changed migratory and metastatic properties. Genome-wide transcriptome analysis revealed that c-Src(mt) deregulated the expression levels of about 430 mRNAs whose gene products are mainly involved in the cellular processes of migration and adhesion, apoptosis and protein synthesis. More than 80% of these genes have previously been linked to cellular migration, while the others play roles, for instance, in RNA transport and splicing processes. Consistent with the transcriptome data, c-Src(mt)-, but not c-Src(wt)-expressing cells showed the capacity to metastasize into mouse lung tissue in vivo. The mRNA expression profile of c-Src(mt)-expressing cells shows significant overlap with that of various primary human tumor samples, perhaps reflecting elevated Src activity in some cancerous cells. Expression of c-Src(mt) lead to elevated migratory potential. We used this model system to analyze the transcriptional changes associated with an invasive cellular phenotype. We identified genes and pathways deregulated by c-Src(mt) as biomarkers with potential interest for diagnostics or therapy of metastatic cells.

Published
2016

4. Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies

Author

Thomalla, D., Beckmann, L., Grimm, C., Oliverio, M., Meder, L., Herling, C.D., Nieper, P., Feldmann, T., Merkel, O., Lorsy, E., da Palma Guerreiro, A., von Jan, J., Kisis, I., Wasserburger, E., Claasen, J., Faitschuk-Meyer, E., Altmüller, J., Nürnberg, P., Yang, T.-P., Lienhard, M., Herwig, R., Kreuzer, K.-A., Pallasch, C.P., Büttner, R., Schäfer, S.C., Hartley, J., Abken, H., Peifer, M., Kashkar, H., Knittel, G., Eichhorst, B., Ullrich, R.T., Herling, M., Reinhardt, H.C., Hallek, M., Schweiger, M.R., and Frenzel, L.P.

Abstract

The BCL2 inhibitor venetoclax has been approved to treat different hematological malignancies. Since there is no common genetic alteration causing resistance to venetoclax in CLL and B cell lymphoma, we asked if epigenetic events might be involved in venetoclax resistance. Therefore, we employed whole exome sequencing, methylated DNA immunoprecipitation sequencing and genome wide CRISPR/Cas9 screening to investigate venetoclax resistance in aggressive lymphoma and high-risk CLL patients. We identified a regulatory CpG island within the PUMApromoter which is methylated upon venetoclax treatment, mediating PUMAdownregulation on transcript and protein level. PUMAexpression and sensitivity towards venetoclax can be restored by inhibition of methyltransferases. We can demonstrate that loss of PUMA results in metabolic reprogramming with higher OXPHOS and ATP production, resembling the metabolic phenotype that is seen upon venetoclax resistance. While PUMA loss is specific for acquired venetoclax resistance but not for acquired MCL1 resistance and is not seen in CLL patients after chemotherapy-resistance, BAX is essential for sensitivity towards both venetoclax and MCL1 inhibition. As we found loss of BAX in Richter’s syndrome patients after venetoclax failure, we defined BAX-mediated apoptosis to be critical for drug resistance but not for disease progression of CLL into aggressive DLBCL in vivo. A compound screen revealed TRAIL-mediated apoptosis as a target to overcome BAX deficiency. Furthermore, antibody or CAR T cells eliminated venetoclax resistant lymphoma cells, paving a clinically applicable way to overcome venetoclax resistance.

Published
2024
Full Text
View/download PDF

6. The Interlaboratory RObustness of Next-generation sequencing (IRON) study: a deep sequencing investigation of TET2, CBL and KRAS mutations by an international consortium involving 10 laboratories.

Author

Kohlmann, A., Klein, H.U., Weissmann, S., Bresolin, S., Chaplin, T., Cuppens, H., Haschke-Becher, E., Garicochea, B., Grossmann, V., Hanczaruk, B., Hebestreit, K., Gabriel, C., Iacobucci, I., Jansen, J.H., Kronnie, G. Te, Locht, L.T. van de, Martinelli, G., McGowan, K., Schweiger, M.R., Timmermann, B., Vandenberghe, P., Young, B.D., Dugas, M., Haferlach, T., Kohlmann, A., Klein, H.U., Weissmann, S., Bresolin, S., Chaplin, T., Cuppens, H., Haschke-Becher, E., Garicochea, B., Grossmann, V., Hanczaruk, B., Hebestreit, K., Gabriel, C., Iacobucci, I., Jansen, J.H., Kronnie, G. Te, Locht, L.T. van de, Martinelli, G., McGowan, K., Schweiger, M.R., Timmermann, B., Vandenberghe, P., Young, B.D., Dugas, M., and Haferlach, T.

Abstract

1 december 2011, Item does not contain fulltext, Massively parallel pyrosequencing allows sensitive deep sequencing to detect molecular aberrations. Thus far, data are limited on the technical performance in a clinical diagnostic setting. Here, we investigated as an international consortium the robustness, precision and reproducibility of amplicon next-generation deep sequencing across 10 laboratories in eight countries. In a cohort of 18 chronic myelomonocytic leukemia patients, mutational analyses were performed on TET2, a frequently mutated gene in myeloproliferative neoplasms. Additionally, hotspot regions of CBL and KRAS were investigated. The study was executed using GS FLX sequencing instruments and the small volume 454 Life Sciences Titanium emulsion PCR setup. We report a high concordance in mutation detection across all laboratories, including a robust detection of novel variants, which were undetected by standard Sanger sequencing. The sensitivity to detect low-level variants present with as low as 1-2% frequency, compared with the 20% threshold for Sanger-based sequencing is increased. Together with the output of high-quality long reads and fast run time, we demonstrate the utility of deep sequencing in clinical applications. In conclusion, this multicenter analysis demonstrated that amplicon-based deep sequencing is technically feasible, achieves high concordance across multiple laboratories and allows a broad and in-depth molecular characterization of cancer specimens with high diagnostic sensitivity.

Published
2011

7. Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome.

Author

Krawitz, P.M., Schweiger, M.R., Rodelsperger, C., Marcelis, C.L.M., Kolsch, U., Meisel, C., Stephani, F., Kinoshita, T., Murakami, Y., Bauer, S., Isau, M., Fischer, A., Dahl, A., Kerick, M., Hecht, J., Kohler, S., Jager, M. de, Grunhagen, J., Condor, B.J. de, Doelken, S., Brunner, H.G., Meinecke, P., Passarge, E., Thompson, M.D., Cole, D.E., Horn, D., Roscioli, T., Mundlos, S., Robinson, P.N., Krawitz, P.M., Schweiger, M.R., Rodelsperger, C., Marcelis, C.L.M., Kolsch, U., Meisel, C., Stephani, F., Kinoshita, T., Murakami, Y., Bauer, S., Isau, M., Fischer, A., Dahl, A., Kerick, M., Hecht, J., Kohler, S., Jager, M. de, Grunhagen, J., Condor, B.J. de, Doelken, S., Brunner, H.G., Meinecke, P., Passarge, E., Thompson, M.D., Cole, D.E., Horn, D., Roscioli, T., Mundlos, S., and Robinson, P.N.

Abstract

1 oktober 2010, Contains fulltext : 88212.pdf (publisher's version ) (Closed access), Hyperphosphatasia mental retardation (HPMR) syndrome is an autosomal recessive form of mental retardation with distinct facial features and elevated serum alkaline phosphatase. We performed whole-exome sequencing in three siblings of a nonconsanguineous union with HPMR and performed computational inference of regions identical by descent in all siblings to establish PIGV, encoding a member of the GPI-anchor biosynthesis pathway, as the gene mutated in HPMR. We identified homozygous or compound heterozygous mutations in PIGV in three additional families.

Published
2010

9. Erratum: Campylobacter jejuniimpairs sodium transport and epithelial barrier function via cytokine release in human colon

Author

Bücker, R., Krug, S.M., Moos, V., Bojarski, C., Schweiger, M.R., Kerick, M., Fromm, A., Janßen, S., Fromm, M., Hering, N.A., Siegmund, B., Schneider, T., Barmeyer, C., and Schulzke, J.D.

Abstract

Correction to: Mucosal Immunology, advance online publication 2 August 2017; doi:10.1038/mi.2017.66 The advance online version of this paper was inadvertently published with Figures 2 and 4 in black and white. The color versions appear below and in the issue version of the paper in print and online.The publisher regrets the error.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results