Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Genomic alterations and gene expression in primary diffuse large B cell lymphomas of immune privileged sites

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Marije Booman

PROVIDER: E-GEOD-10524 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genomic alterations and gene expression in primary diffuse large B-cell lymphomas of immune-privileged sites: the importance of apoptosis and immunomodulatory pathways.

Booman M M Szuhai K K Rosenwald A A Hartmann E E Kluin-Nelemans Hc H de Jong D D Schuuring E E Kluin Pm P

The Journal of pathology 20081001 2

Primary diffuse large B-cell lymphomas of different immune-privileged sites (IP-DLBCLs) 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, nine central nervous system (CNS), and 15 nodal DLBCLs using ar ...[more]

PMID: 18729069

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Project description:Introduction: In breast cancers, the basal-like subtype has high levels of genomic instability relative to other breast cancer subtypes with many basal-like-specific regions of aberration. There is evidence that this genomic instability extends to smaller scale genomic aberrations as well, as shown by a previously described micro-event in the PTEN gene in the Basal-like SUM149 breast cancer cell line. Methods: We sought to identify if small regions of genomic change exist by using a high density, gene centric Comparative Genomic Hybridizations (CGH) array on both cell lines and primary tumors. A custom Agilent tiling array for CGH (244,000 probes, 200bp tiling resolution) was created to identify small regions of genomic change and was focused on previously identified basal-like-specific, and general cancer genes. Tumor genomic DNA from 94 patients and 2 breast cancer cell lines was labeled and hybridized to these arrays. Aberrations were called using SWITCHdna and the smallest 25% of SWITCHdna-defined genomic segments being called micro-aberrations (<64 contiguous probes, ~ <15kb). Results: Our data showed that primary tumor breast cancer genomes frequently contained areas of small-scale copy number gains and losses, termed micro-aberrations, which are undetectable using lower-density genome-wide platforms. The basal-like subtype exhibited the highest incidence of these events. These micro-aberrations sometimes altered expression of the involved gene as suggested by data from microarray and mRNA-seq studies. We confirmed the presence of the PTEN micro-amplification in SUM149 and by mRNA-seq showed that this resulted in loss of expression of all exons downstream of this event. Micro-aberrations disproportionately affected the 5’ regions of the affected genes, including the promoter region, and a high frequency of micro-aberrations was associated with poor survival outcomes. Conclusion: Using a high probe density, gene-centric aCGH microarray, we present evidence of small-scale genomic aberrations that contribute to gene inactivation, and thus, genomic instability and tumor formation through a mechanism not detected using conventional copy number analyses. reference x sample

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Dataset Information

Genomic alterations and gene expression in primary diffuse large B cell lymphomas of immune privileged sites

Publications

Genomic alterations and gene expression in primary diffuse large B-cell lymphomas of immune-privileged sites: the importance of apoptosis and immunomodulatory pathways.

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