Adult High Grade B-cell Lymphoma with Burkitt Lymphoma Signature: Genomic features and Potential Therapeutic Targets
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PROVIDER: PRJNA707396 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression profiling of RNA and SNP array profiling of DNA was performed on Burkitt lymphoma samples to identify genes and pathways affected by DNA copy number alterations and expression changes.
2021-03-09 | GSE168422 | 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.
2011-01-20 | GSE26673 | GEO
Project description:The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24, and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes. Mutations in genes promoting the tonic B-cell receptor (BCR)→PI3K pathway (TCF3 and ID3) did not differ by age, whereas effectors of chronic BCR→NF-κB signaling were associated with adult-mBL. A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation profile similar to mBL. These double-hit lymphomas may have arisen from a tumor precursor that acquired both BCL2 and MYC translocations and/or KMT2D (MLL2) mutation. Gain/amplification of MIR17HG and its paralogue loci was observed in 50% of adult-mBL. In vitro studies suggested miR-17∼92's role in constitutive activation of BCR signaling and sensitivity to ibrutinib. Overall integrative analysis identified an interrelated gene network affected by copy number and mutation, leading to disruption of the p53 pathway and the BCR→PI3K or NF-κB activation, which can be further exploited in vivo by small-molecule inhibitors for effective therapy in adult-mBL.
| S-EPMC5649549 | biostudies-literature
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: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.
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Project description:Burkitt Lymphoma cell lines were established and used for methylome profiling with Illumina HM450 beadchip
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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. Gene expression profiling on 21 Burkitt lymphomas was performed using standard Affymetrix protocols as described previously. Briefly, 1 μg of total RNA was reverse transcribed, using oligo(dT) primer to synthesize cDNA. T7 primer was used for in vitro transcription, resulting in labeled cRNA, which was fragmented and hybridized to Affymetrix Whole-Genome Gene 1.0 ST microarrays. Microarrays were washed and scanned, and the data were normalized as described previously.
2013-07-01 | E-GEOD-48435 | biostudies-arrayexpress
Project description:Burkitt lymphoma (BL) is the most frequent B-cell lymphoma in pediatric patients. While most patients are currently cured, a fraction of them are resistant to therapy. In order to investigate BL heterogeneity and the features distinguishing the non-responders (NR) to therapy, we analyzed pediatric EBV-negative BL specimens collected at diagnosis by single-cell (sc)-transcriptomics. Analysis of the non-tumor component revealed a predominance of immune cell infiltrates and a small representation of fibroblasts that was enriched in NR. Tumor cells displayed patient-specific features, as well as subpopulations that were common to most patients and expressed transcripts related to cell cycle, signaling pathways and cell-of-origin signatures.
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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
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