IG-MYC-positive neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE114210 | GEO | 2018/10/08
REPOSITORIES: GEO
Similar Datasets
Project description:IG-MYC-positive neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas
| PRJNA470587 | ENA
Project description:MYC translocations are the biologic hallmark of Burkitt lymphomas but also occur in other mature B-cell lymphomas. If accompanied by chromosomal breaks targeting the BCL2 and/or BCL6 oncogenes, these MYC translocation-positive (MYC+) lymphomas are called double-hit lymphomas (DHLs); otherwise, the term single-hit lymphoma (SHL) is applied. In order to characterize the biologic features of these MYC+ lymphomas other than Burkitt lymphomas, we explored, after exclusion of molecular Burkitt lymphoma (mBL) as defined by gene expression profiling (GEP), the molecular, pathological and clinical aspects of 80 MYC translocation (MYC+) lymphomas (31 SHL, 26 BCL2+/MYC+, 14 BCL6+/MYC+, 6 BCL2+/BCL6+/MYC+ and 3 MYC+ lymphomas with unknown BCL6 status). Comparison of SHL and DHL revealed no difference in frequency of MYC partner (IG/non-IG), genomic complexity or MYC expression and no differences in GEP. DHL showed a more frequent GCB-like GEP and higher IGH and MYC mutation rates. GEP revealed 130 differentially expressed genes between BCL6+/MYC+ and BCL2+/MYC+ DHL. BCL2+/MYC+ DHL showed a more frequent GCB-like GEP. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In contrast to mBL and lymphomas without MYC break, SHL and DHL patients had similar poor outcome. Our data suggest that after excluding mBL, MYC+ lymphomas could be biologically widely lumped without further need for subclassification.
2013-12-31 | GSE44164 | GEO
Project description:The WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue notes instances of Burkitt lymphoma/leukemia (BL) with IG-MYC rearrangement displaying a B-cell precursor immunophenotype (termed herein "preBLL"). To characterize the molecular pathogenesis of preBLL, we investigated 13 preBLL cases (including 1 cell line), of which 12 were analyzable using genome, exome, and targeted sequencing, imbalance mapping, and DNA methylation profiling. In 5 patients with reads across the IG-MYC breakpoint junctions, we found evidence that the translocation derived from an aberrant VDJ recombination, as is typical for IG translocations arising in B-cell precursors. Genomic changes like biallelic IGH translocations or VDJ rearrangements combined with translocation into the VDJ region on the second allele, potentially preventing expression of a productive immunoglobulin, were detected in 6 of 13 cases. We did not detect mutations in genes frequently altered in BL, but instead found activating NRAS and/or KRAS mutations in 7 of 12 preBLLs. Gains on 1q, recurrent in BL and preB lymphoblastic leukemia/lymphoma (pB-ALL/LBL), were detected in 7 of 12 preBLLs. DNA methylation profiling showed preBLL to cluster with precursor B cells and pB-ALL/LBL, but apart from BL. We conclude that preBLL genetically and epigenetically resembles pB-ALL/LBL rather than BL. Therefore, we propose that preBLL be considered as a pB-ALL/LBL with recurrent genetic abnormalities.
| S-EPMC6251006 | biostudies-literature
Project description:MYC translocations are the biologic hallmark of Burkitt lymphomas but also occur in other mature B-cell lymphomas. If accompanied by chromosomal breaks targeting the BCL2 and/or BCL6 oncogenes, these MYC translocation-positive (MYC+) lymphomas are called double-hit lymphomas (DHLs); otherwise, the term single-hit lymphoma (SHL) is applied. In order to characterize the biologic features of these MYC+ lymphomas other than Burkitt lymphomas, we explored, after exclusion of molecular Burkitt lymphoma (mBL) as defined by gene expression profiling (GEP), the molecular, pathological and clinical aspects of 80 MYC translocation (MYC+) lymphomas (31 SHL, 26 BCL2+/MYC+, 14 BCL6+/MYC+, 6 BCL2+/BCL6+/MYC+ and 3 MYC+ lymphomas with unknown BCL6 status). Comparison of SHL and DHL revealed no difference in frequency of MYC partner (IG/non-IG), genomic complexity or MYC expression and no differences in GEP. DHL showed a more frequent GCB-like GEP and higher IGH and MYC mutation rates. GEP revealed 130 differentially expressed genes between BCL6+/MYC+ and BCL2+/MYC+ DHL. BCL2+/MYC+ DHL showed a more frequent GCB-like GEP. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In contrast to mBL and lymphomas without MYC break, SHL and DHL patients had similar poor outcome. Our data suggest that after excluding mBL, MYC+ lymphomas could be biologically widely lumped without further need for subclassification. 32 diffuse large B-cell lymphoma samples were hybridized to HG-U133A Affymetrix GeneChips. In addition, this study contains 30 already published samples, which contribute to GSE4475 (Hummel et al. 2006 (PMID 16760442)), as well as 18 already published samples from GSE22470 (Salaverria et al. 2011 (PMID 21487109)). No re-normalisation of the published samples was performed. The complete dataset representing: (1) the 32 diffuse large B-cell lymphoma Samples, (2) the 30 Samples from GSE4475 and (3) the 18 Samples from GSE22470, is linked below as a supplementary file
2013-12-31 | E-GEOD-44164 | biostudies-arrayexpress
Project description:By whole-genome, exome, transcriptome and methylome sequencing of four proto-typical Burkitt lymphomas (BL) with IG-MYC translocation we identified seven recurrently mutated genes including ID3. In an extended cohort, 36/53 (68%) molecularly-defined BL carried potentially damaging mutations of ID3 which were enriched at somatic hypermutation motifs. Only 6/47 (13%) other IG-MYC-positive B-cell lymphomas carried ID3 mutations suggesting cooperation of ID3 inactivation and IG-MYC translocation to be a hallmark of Burkitt lymphomagenesis.
| EGAS00001000271 | EGA
Project description:Burkitt lymphoma is the commonest cancer in children in Africa. We compared the gene expression profiles of African Burkitt lymphoma patients with those of cases presented in Western countries in both immunocompetent (sporadic Burkitt lymphoma) and HIV-infected patients (immunodeficiency associated Burkitt lymphoma). We used microarrays to detail the global programme of gene expression in different subtypes of Burkitt lymphoma.
2011-01-20 | GSE26673 | GEO
Project description:Burkitt lymphoma is the commonest cancer in children in Africa. We compared the gene expression profiles of African Burkitt lymphoma patients with those of cases presented in Western countries in both immunocompetent (sporadic Burkitt lymphoma) and HIV-infected patients (immunodeficiency associated Burkitt lymphoma). We used microarrays to detail the global programme of gene expression in different subtypes of Burkitt lymphoma. Lymph-node biopsies were collected at diagnosis. Gene expression profiles were generated with the Affymetrix HG U133 2.0 plus microarray
2011-01-20 | E-GEOD-26673 | biostudies-arrayexpress
Project description:The distinction between the Burkitt lymphoma and diffuse large B-cell lymphoma is imprecise using current diagnostic criteria. We applied transcriptional and genomic profiling to molecularly define Burkitt lymphoma. Gene expression profiling employing Affymetrix GeneChips (U133A) was performed in 220 mature aggressive B-cell lymphomas, including a core group of eight Burkitt lymphomas, which fulfilled all diagnostic criteria of the WHO classification. A molecular signature of Burkitt lymphoma was generated. Chromosomal abnormalities were detected by interphase fluorescence in-situ hybridization and array comparative genomic hybridization. The molecular Burkitt lymphoma signature identified 44 cases. Fifteen of these cases lacked a morphology typical for Burkitt/Burkitt-like lymphoma. The vast majority (88%) of the 176 lymphomas without the molecular Burkitt lymphoma signature represented diffuse large B-cell lymphomas. In 20% of these cases a MYC break was detectable which was associated with complex chromosomal changes. Our molecular definition of Burkitt lymphoma sharpens and extends the spectrum of Burkitt lymphoma. In mature aggressive B-cell lymphomas without a Burkitt lymphoma signature, a chromosomal break in the MYC locus proved to be associated with adverse clinical outcome. Experiment Overall Design: 220 diffuse large B-cell lymphoma and Burkitt lymphoma samples hybridized to 221 HGU133A Affymetrix GeneChips
2008-06-13 | E-GEOD-4475 | biostudies-arrayexpress
Project description:Burkitt Lymphoma patient samples using gene expression to create a molecular definition of the disease. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Keywords: clinical history design Samples were obtained from patients with Burkitt lymphoma and gene expression profiling was used to create a molecular definition of the disease. The molecular definition was then used to predict the disease in an independent set of patients with atypical Burkitt lymphoma and diffuse large B cell lymphoma.
2006-07-04 | E-GEOD-4732 | biostudies-arrayexpress
Project description:Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.
2013-07-01 | GSE48435 | GEO