Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Variability in functional p53 reactivation by Prima-1Met/APR-246 in Ewing sarcoma

ABSTRACT: Though p53 mutations are rare in Ewing sarcoma, there is a strong indication that p53-mutant tumors form a particularly bad prognosis group. As such, novel treatment strategies are warranted that would specifically target and eradicate tumor cells containing mutant-p53 in this subset of ES patients. PRIMA-1Met/APR-246 is a small organic molecule which has been shown to restore tumor suppressor function primarily to mutant p53 and to also induce cell death in various cancer cell types. We analyzed the apoptosis inducibility on Ewing sarcoma cells harbouring different p53 mutations upon exposure to APR-246. Gene expression profiles of three STA-ET-7 cell lines established from the same patient at different stages of the disease was assessed by microarray analysis as these cell lines responded variably to APR-246.

ORGANISM(S): Homo sapiens

SUBMITTER: Maximilian Kauer

PROVIDER: E-GEOD-49967 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Variability in functional p53 reactivation by PRIMA-1(Met)/APR-246 in Ewing sarcoma.

Aryee D N T DN Niedan S S Ban J J Schwentner R R Muehlbacher K K Kauer M M Kofler R R Kovar H H

British journal of cancer 20131015 10

<h4>Background</h4>Though p53 mutations are rare in ES, there is a strong indication that p53 mutant tumours form a particularly bad prognostic group. As such, novel treatment strategies are warranted that would specifically target and eradicate tumour cells containing mutant p53 in this subset of ES patients.<h4>Methods</h4>PRIMA-1(Met), also known as APR-246, is a small organic molecule that has been shown to restore tumour-suppressor function primarily to mutant p53 and also to induce cell de ...[more]

PMID: 24129240

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Project description:Background Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin lymphoma. However, little is known regarding epigenetic similarities between classical Hodgkin lymphoma and plasma cell myeloma cells, both of which share an extinction of the gene expression program of mature B-cells. Design and methods Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA-PCR for selected genes. Epigenetic modifications were compared to gene expression data. Results B-cell characteristic genes were hypoacetylated in classical Hodgkin lymphoma and plasma cell myeloma cell lines, as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin lymphoma and plasma cell myeloma cell lines, such as IFR4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected B-cell characteristic genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin lymphoma as compared to plasma cell myeloma. Conclusion Our epigenetic data support the view that classical Hodgkin lymphoma is characterized by an abortive plasma cell differentiation with a down-regulation of B-cell characteristic genes but without activation of most plasma cell typical genes. Gene expression analysis of Hodgkin lymphoma (cHL) and B-cell lines: Microarray data for three Hodgkin lymphoma cell lines (KM-H2, L1236, L428) and the B-cell line Namalwa that were published previously by our group (GEO accession GSE8388) were analyzed together with newly generated data for the B-cell lines SU-DHL4 and SU-DHL6. For all cell lines, RNA was isolated according to standard protocols (Qiagen, Hilden, Germany) and used for Affymetrix GeneChip hybridization (HG-U133A). Microarrays were normalized using RMA, and differential expression was calculated using moderated t-test. The gene expression profiles of the cell lines were generated in duplicates.

Project description:Background Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin lymphoma. However, little is known regarding epigenetic similarities between classical Hodgkin lymphoma and plasma cell myeloma cells, both of which share an extinction of the gene expression program of mature B-cells. Design and methods Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA-PCR for selected genes. Epigenetic modifications were compared to gene expression data. Results B-cell characteristic genes were hypoacetylated in classical Hodgkin lymphoma and plasma cell myeloma cell lines, as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin lymphoma and plasma cell myeloma cell lines, such as IFR4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected B-cell characteristic genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin lymphoma as compared to plasma cell myeloma. Conclusion Our epigenetic data support the view that classical Hodgkin lymphoma is characterized by an abortive plasma cell differentiation with a down-regulation of B-cell characteristic genes but without activation of most plasma cell typical genes. Gene expression analysis of plasma cell myeloma (PCM) and B-cell lines: Microarray data of the B-cell line Namalwa that was published previously by our group (GEO accession number GSE8388) was analyzed together with newly generated data for the B-cell lines SU-DHL4 and SU-DHL6 (duplicates) and three PCM cell lines (L363, U266, LP1). For all cell lines, RNA was isolated according to standard protocols (Qiagen, Hilden, Germany) and used for Affymetrix GeneChip hybridization (HG-U133A). Microarrays were normalized using RMA, and differential expression was calculated using moderated t-test.

Dataset Information

Variability in functional p53 reactivation by Prima-1Met/APR-246 in Ewing sarcoma

Publications

Variability in functional p53 reactivation by PRIMA-1(Met)/APR-246 in Ewing sarcoma.

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