Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Molecular Classification of AIDS-Related Lymphomas [including third-party data]

ABSTRACT: Gene expression profiling (GEP) of ARL patient samples was done to determine whether gene expression signatures derived from HIV- lymphomas retained their ability to molecularly classify HIV+ lymphomas. The GEP-based predictors robustly classified ARL tumors, distinguishing molecular Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as well as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) molecular subtypes of DLBCL. Gene expression profiles were used to identify coordinately regulated gene sets and pathways that differ between HIV+ and HIV- lymphomas of corresponding molecular subtype. Frozen tumor biopsies were obtained from 20 HIV-positive patients with an AIDS-defining lymphoma. Cases were ascertained at the University of Nebraska Medical Center and through the NCI AIDS and Cancer Specimen Resource tumor bank. Sufficient RNA for hybridization to Affymetrix U133 plus 2 arrays was obtained on 17 ARL cases. Details of all 20 HIV-positive patients can be found in the supplementary file below. Third party array data from HIV- lymphomas of corresponding molecular subtype were used for the comparison and molecular classification of the HIV+ cases in this study. The third party HIV- lymphoma samples include the following. [1] HIV- lymphoma, BL cases: 84 samples profiled on the Affymetrix HG U133 Plus 2 array. The data are publicly available on the website companion to Dave et al. NEJM 2006; Volume 354:13-24 (http://llmpp.nih.gov/BL/) and were used 'as is' (ie, not reanalyzed). [2] HIV- lymphoma, DLBCL cases: 200 of the 414 cases in Series GSE10846 (listed in the supplementary file below). These included all R-CHOP treated cases of either ABC or GCB subtype. These data were also used as is. These data were published in Lenz et al. NEJM 2008; Volume 359: 2313-2323.

ORGANISM(S): Homo sapiens

SUBMITTER: Karen Deffenbacher

PROVIDER: E-GEOD-17372 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Recurrent chromosomal alterations in molecularly classified AIDS-related lymphomas: an integrated analysis of DNA copy number and gene expression.

Deffenbacher Karen E KE Iqbal Javeed J Liu Zhongfeng Z Fu Kai K Chan Wing C WC

Journal of acquired immune deficiency syndromes (1999) 20100501 1

HIV-infected individuals have a significantly increased risk of developing an aggressive B-cell Non-Hodgkin Lymphoma relative to HIV(-) persons. Due to their aggressive nature, AIDS-related lymphomas (ARL) can also be more difficult to classify. Genetic abnormalities are known to play a significant role in HIV(-) lymphomagenesis. To aid in case classification and identify key pathogenetic events in ARL, we analyzed gene expression data and somatic DNA copy number changes by high-resolution array ...[more]

PMID: 20216076

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Project description:The most frequent mature aggressive B-cell lymphomas are diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Patients suffering from molecularly defined BL (mBL) but treated with a regimen developed for DLBCL show an unfavorable outcome compared to mBL treated with chemotherapy regimens for BL. Distinguishing BL from DLBCL by conventional histopathology is challenging in lymphomas that have features common to both diseases (aggressive B-cell lymphoma unclassifiable with features of DLBCL and BL [intermediates]). Moreover, DLBCL are a heterogeneous group of lymphomas comprising distinct molecular subtypes: the activated B-cell (ABC)-like, the germinal center B-cell-like (GCB) and the unclassifyable subtype as defined by gene expression profiling (GEP). Attempts to replace GEP with techniques applicable to formalin-fixed paraffin-embedded (FFPE) tissue led to algorithms for immunohistochemical stainings (IHS). Disappointingly, the algorithms yielded conflicting results with respect to their prognostic potential, raising concerns about their validity. Furthermore, IHS algorithms did not provide a fully resolved classification: They did not identify mBL; nor did they separate ABC from unclassified DLBCL. We used digital multiplexed gene expression (DMGE) with FFPE derived RNA to classify agressive B-cell lymphomas. Our assay comprised only 30 genes (10 for the detection of mBL and 20 for the detection of ABC and GCB). We chose these genes by reanalysis of the microarray data reported in a previous study. 39 samples from mature aggressive B-cell lymphomas were analyzed using DMGE (nCounter, NanoString Technologies Inc., Seattle, WA, USA) of FFPE- and fresh-frozen derived RNA. All cases were previously characterized by the Molecular Mechanisms of Malignant Lymphoma (MMML) consortium using the Affymetrix GeneChip technology (gold standard of classification). 29 diffuse large B-Cell lymphoma samples were hybridized to HGU133A Affymetrix GeneChips. In addition, this study contains 22 already published samples whereas 11 of them contribute to GSE22470, 6 contribute to GSE10172, 3 to GSE44164 and 2 to GSE4475. No re-normalisation of published samples was performed. The dataset representing: (1) 11 samples from GSE22470, (2) 6 samples from GSE10172, (3) 3 samples from GSE44164 and (4) 2 samples from GSE4475 is linked below as a supplementary file.

Project description:The most frequent mature aggressive B-cell lymphomas are diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Patients suffering from molecularly defined BL (mBL) but treated with a regimen developed for DLBCL show an unfavorable outcome compared to mBL treated with chemotherapy regimens for BL. Distinguishing BL from DLBCL by conventional histopathology is challenging in lymphomas that have features common to both diseases (aggressive B-cell lymphoma unclassifiable with features of DLBCL and BL [intermediates]). Moreover, DLBCL are a heterogeneous group of lymphomas comprising distinct molecular subtypes: the activated B-cell (ABC)-like, the germinal center B-cell-like (GCB) and the unclassifyable subtype as defined by gene expression profiling (GEP). Attempts to replace GEP with techniques applicable to formalin-fixed paraffin-embedded (FFPE) tissue led to algorithms for immunohistochemical stainings (IHS). Disappointingly, the algorithms yielded conflicting results with respect to their prognostic potential, raising concerns about their validity. Furthermore, IHS algorithms did not provide a fully resolved classification: They did not identify mBL; nor did they separate ABC from unclassified DLBCL. 29 diffuse large B-Cell lymphoma samples were hybridized to HGU133A Affymetrix GeneChips. In addition, this study contains 22 already published samples whereas 11 of them contribute to GSE22470, 6 contribute to GSE10172, 3 to GSE44164 and 2 to GSE4475. No re-normalisation of published samples was performed. We used digital multiplexed gene expression (DMGE) with FFPE derived RNA to classify agressive B-cell lymphomas. Our assay comprised only 30 genes (10 for the detection of mBL and 20 for the detection of ABC and GCB). We chose these genes by reanalysis of the microarray data reported in a previous study. 39 samples from mature aggressive B-cell lymphomas were analyzed using DMGE (nCounter, NanoString Technologies Inc., Seattle, WA, USA) of FFPE- and fresh-frozen derived RNA. All cases were previously characterized by the Molecular Mechanisms of Malignant Lymphoma (MMML) consortium using the Affymetrix GeneChip technology (gold standard of classification). Please note that there are total 40 FFPE-derived and 50 fresh-frozen derived samples, with 39 samples derived from both materials (allowing direct comparison).

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Dataset Information

Molecular Classification of AIDS-Related Lymphomas [including third-party data]

Publications

Recurrent chromosomal alterations in molecularly classified AIDS-related lymphomas: an integrated analysis of DNA copy number and gene expression.

Similar Datasets

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