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:To characterize the genetic alterations in lymphomas in immune-privileged sites (IP-DLBCLs), we performed whole-genome sequencing (WGS) of 22 primary central nervous system lymphomas (PCNSLs), 8 primary testicular lymphomas (PTLs) and 6 secondary CNS lymphomas.
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.
