High-resolution genomic profiling of marginal zone B-cell lymphomas and variants
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36311 | GEO | 2013/01/11
SECONDARY ACCESSION(S): PRJNA153347
REPOSITORIES: GEO
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Project description:We studied marginal zone B-cell lymphomas of the gastrointestinal tract including seven small cell MALT lymphomas, eight composite lymphomas and thirteen large cell variants using SNP-array profiling. We found an increase of genomic complexity with lymphoma progression, and could identify gains of prominent (proto)oncogenes REL, ETS1, PTPN1, PTEN and KRAS that were associated exclusively with the large cell presentation of MALT lymphoma. Losses of ADAM3A and SCAPER, as well as gains of SIRPB1 occur during progression from small cell to large cell lymphoma. In two case studies, we examined lymphoma progression comparing two different regions of the same tumor and material acquired at two different time points from another lymphoma. Our analyses reveal genomic heterogeneity in both cases, supporting the theory of an oligoclonal tumor evolution model for MALT lymphomas and its variants. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved tumor samples. Copy number and loss of heterozygosity analysis of Affymetrix GenomeWide SNP 6.0 arrays was performed for 7 small cell MALT lymphomas, 8 large cell areas of Composite lymphomas and 13 large cell variants. Two independant hybridizations of one of the small cell MALT lymphoma and one of the large cell areas of Composite lymphoma Samples were performed.
2013-01-11 | E-GEOD-36311 | biostudies-arrayexpress
Project description:Marginal zone B-cell lymphomas (MZL) have been divided into three distinct subtypes (extranodal MZL of MALT type, nodal MZL; splenic MZL). Nevertheless, the relationship between them is still unclear. We performed a comprehensive analysis of genomic DNA copy number changes in a very large series of MZL cases with the aim of addressing this question. Samples from 218 MZL patients (25 nodal, 57 MALT, 134 splenic and two not better specified MZL) were analyzed with the Affymetrix Human Mapping 250K SNP arrays, and the data combined with matched gene expression in 33/218 cases. MALT lymphoma presented significantly more frequently gains at 3p, 6p, 18p and del(6q23) (TNFAIP3/A20), whilst splenic MZL was associated with del(7q31), del(8p). Nodal MZL did not show statistically significant differences when compared with MALT lymphoma while lacked the splenic MZL-related 7q losses. Gains of 3q and 18q gains were common to all three subtypes. Del(8p) was often present together with del(17p) (TP53). While del(17p) did not determine a worse outcome and del(8p) was only of borderline significance, the presence of both deletions had a highly significant negative impact on the outcome of splenic MZL.
2011-02-01 | GSE24881 | GEO
Project description:Comparison of gene expression profiling analysis of bone marrow isolated CD34+ cells from patients with MALT lymphoma vs. healthy individuals revealed a large number of differentially expressed genes that included NF-kB target genes, genes involved in inflamatory signalling and immunoglobulin genes, suggesting an early lymphoid B-cell priming. Chromosomal translocations involving MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. However, targeting these translocations to mouse B-cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1+Lin- hematopoietic stem/progenitor cells (HS/PCs), leading to the development of tumors recapitulating the clinical, histopathological and molecular features of human MALT lymphomas. Ablation of the p53 gene induced transformation of MALT lymphoma to diffuse large-cell lymphoma of activated B-cell type (ABC-DLBCL). Human CD34+ cells isolated from MALT lymphoma patients displayed an abnormal transcriptional program that was shared by MALT lymphoma cells, transgenic mouse Sca1+Lin- cells and Sca1-MALT1-induced lymphomas. Our study shows that MALT lymphoma can be modeled in mice by targeting MALT1 oncogene to HS/PCs.
2012-07-10 | GSE34015 | GEO
Project description:Marginal zone B-cell lymphomas (MZL) have been divided into three distinct subtypes (extranodal MZL of MALT type, nodal MZL; splenic MZL). Nevertheless, the relationship between them is still unclear. We performed a comprehensive analysis of genomic DNA copy number changes in a very large series of MZL cases with the aim of addressing this question. Samples from 218 MZL patients (25 nodal, 57 MALT, 134 splenic and two not better specified MZL) were analyzed with the Affymetrix Human Mapping 250K SNP arrays, and the data combined with matched gene expression in 33/218 cases. MALT lymphoma presented significantly more frequently gains at 3p, 6p, 18p and del(6q23) (TNFAIP3/A20), whilst splenic MZL was associated with del(7q31), del(8p). Nodal MZL did not show statistically significant differences when compared with MALT lymphoma while lacked the splenic MZL-related 7q losses. Gains of 3q and 18q gains were common to all three subtypes. Del(8p) was often present together with del(17p) (TP53). While del(17p) did not determine a worse outcome and del(8p) was only of borderline significance, the presence of both deletions had a highly significant negative impact on the outcome of splenic MZL. Copy number analysis of Affymetrix 250K Nsp SNP arrays was performed for a total of 218 MZL samples were analyzed by high resolution genome wide-DNA profiling: 57 MALT lymphoma, 134 splenic MZL, 25 nodal MZL and two MZL where allocation to a specific category was not possible.
2011-02-01 | E-GEOD-24881 | biostudies-arrayexpress
Project description:Comparison of gene expression profiling analysis of bone marrow isolated CD34+ cells from patients with MALT lymphoma vs. healthy individuals revealed a large number of differentially expressed genes that included NF-kB target genes, genes involved in inflamatory signalling and immunoglobulin genes, suggesting an early lymphoid B-cell priming. Chromosomal translocations involving MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. However, targeting these translocations to mouse B-cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1+Lin- hematopoietic stem/progenitor cells (HS/PCs), leading to the development of tumors recapitulating the clinical, histopathological and molecular features of human MALT lymphomas. Ablation of the p53 gene induced transformation of MALT lymphoma to diffuse large-cell lymphoma of activated B-cell type (ABC-DLBCL). Human CD34+ cells isolated from MALT lymphoma patients displayed an abnormal transcriptional program that was shared by MALT lymphoma cells, transgenic mouse Sca1+Lin- cells and Sca1-MALT1-induced lymphomas. Our study shows that MALT lymphoma can be modeled in mice by targeting MALT1 oncogene to HS/PCs. 10 samples were analyzed of which 5 are CD34+ cells sorted from the bone marrow of MALT patients and are compared to the other 5 CD34+ cells sorted from the bone marrow of healthy donors.
2012-07-09 | E-GEOD-34015 | biostudies-arrayexpress
Project description:Attempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NF-kappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies. Keywords: lymphoma profiling, MALT lymphoma
2012-07-10 | GSE25638 | GEO
Project description:Extranodal marginal zone B-cell lymphoma (MZBL) of the mucosa-associated lymphoid tissue (MALT) is an indolent lymphoma mostly affecting the gastrointestinal tract. In the stomach, MZBL of MALT initially has small cell morphology (SC-MZBL) and arises in the background of Helicobacter pylori induced gastritis. Clonal malignant progression to large cell morphology (LC-MZBL) is observed. During this progression an intermediate stage consisting of both the small cell and large cell morphology is present, called "composite lymphoma". To gain insight into the DNA methylation changes associated with progression of gastric MZBL of MALT, we performed genome-wide DNA methylation profiling using the Illumina Infinium MethylationEPIC BeadChip array for 30 microdissected samples of gastric MZBL of MALT.
2021-05-21 | GSE150417 | GEO
Project description:Attempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NF-kappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies. Keywords: lymphoma profiling, MALT lymphoma 97 samples were analized of which 13 were normal B-cell purified subpopulations and 84 lymphoma samples (31 MALT lymphomas, 26 DLBCL, 15 FCL and 12 SMZL)
2012-07-09 | E-GEOD-25638 | biostudies-arrayexpress
Project description:Attempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NFkappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies. Keywords: Genetic modification, wt vs. transgenic, disease analysis, MALT lymphoma
2012-07-10 | GSE25637 | GEO
Project description:Attempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NFkappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies. Keywords: Genetic modification, wt vs. transgenic, MALT1 expression
2012-07-10 | GSE25636 | GEO