Project description:Primary diffuse large B cell lymphomas of different immune-privileged sites (IP-DLBCL) share many clinical and biological features, such as a relatively poor prognosis, preferential dissemination to other immune-privileged sites and deletion of the HLA region, which suggests that IP-DLBCL represents a separate entity. To further investigate the nature of IP-DLBCL, we investigated site-specific genomic aberrations in 16 testicular, 9 central nervous system (CNS) and 15 nodal DLBCL using array-CGH. We also determined minimal common regions of gain and loss. Using robust algorithms, the array-CGH data were combined with gene expression data to explore pathways deregulated by chromosomal aberrations. Keywords: comparative genomic hybridisation, gene expression, tumor type comparison Whole tissue sections of 16 testicular, 9 central nervous system (CNS) and 15 nodal DLBCL were used for isolation of genomic DNA and total RNA. Genomic aberrations were determined using an in house printed CGH array containing ~3700 large genomic insert clones. Gene expression was analyzed on Affymetrix HU133 plus 2.0 oligo arrays. Gene expression data and arrayCGH data were combined using the R program ACE-it.
Project description:Primary diffuse large B cell lymphomas of different immune-privileged sites (IP-DLBCL) share many clinical and biological features, such as a relatively poor prognosis, preferential dissemination to other immune-privileged sites and deletion of the HLA region, which suggests that IP-DLBCL represents a separate entity. To further investigate the nature of IP-DLBCL, we investigated site-specific genomic aberrations in 16 testicular, 9 central nervous system (CNS) and 15 nodal DLBCL using array-CGH. We also determined minimal common regions of gain and loss. Using robust algorithms, the array-CGH data were combined with gene expression data to explore pathways deregulated by chromosomal aberrations. Keywords: comparative genomic hybridisation, gene expression, tumor type comparison
Project description:Loss of human leukocyte antigen (HLA) expression on tumor cells is frequent in diffuse large B cell lymphoma (DLBCL) arising in immune-privileged sites such as the testis and central nervous system and is associated with small homozygous deletions of HLA-DQ/DR and larger hemizygous deletions of the major histocompatibility complex (MHC) region. To better understand the significance of downregulation of HLA class II expression in relation to the homozygous and hemizygous deletions, we analyzed global gene expression patterns in a series of 26 testicular diffuse large B-cell lymphomas (DLBCL) after characterization of these deletions. Low levels of HLA-DR mRNA in whole testicular DLBCL samples were associated with a strong downregulation of numerous immune-related genes specific for T-cells, macrophages, antigen presentation and processing, lymphocyte activation, chemokines and chemokine receptors and the complement system. Interestingly, hemizygous and homozygous deletions in the MHC region did not have any additional impact on global gene expression. Keywords: Gene expression
Project description:The aim of the study was to identify molecular mechanisms involved in high risk diffuse large B-cell lymphomas (diffuse large B-cell lymphomas). <br>51 prospectively collected tumor samples from the patients treated in the Nordic phase II study with dose-dense chemoimmunotherapy followed by systemic CNS prophylaxis were analyzed by high resolution array comparative genomic hybridization (aCGH). <br>The aCGH data were combined with the transcriptomics information from the exon array and the data associated with survival.
Project description:Diffuse large B cell lymphomas (DLBCL) constitute a heterogeneous group of lymphomas in which germinal center B cell-like and activated B cell-like subtypes can be discerned based on pathology, clinical presentation and gene expression patterns. Testicular DLBCL form an immune-privileged site-related subgroup of DLBCL with an unfavorable prognosis. We used cDNA microarray analysis, immunohistochemistry for CD10, Bcl6 and MUM1, and somatic hypermutation analysis of the immunoglobulin heavy chain gene rearrangements to determine the subtype of primary testicular DLBCL. Immunohistochemistry revealed 14/22 testicular DLBCL with an activated B cell-like immunophenotype and 8/22 with an ambiguous immunophenotype co-expressing CD10 and high levels of MUM1. cDNA microarray analysis of these 22 and 4 additional cases showed a uniform activated B cell-like gene expression pattern in both immunophenotypes. Somatic hypermutation analysis showed a very high mutation load in 7 cases tested, but intraclonal heterogeneity was found at low level in only one of these cases. We conclude that primary testicular DLBCL have uniform activated B cell-like subtype characteristics despite a number of cases showing an ambiguous immunophenotype. Keywords: Gene expression
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