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E-GEOD-9992 - Molecular and transcriptional characterization of chromosome 17p loss in chronic lymphocytic leukemia, experiment A

Status
Released on 11 November 2008, last updated on 22 June 2012
Organism
Homo sapiens
Samples (60)
Array (1)
Protocols (7)
Description
Distinct genetic abnormalities such as TP53 deletion at 17p13.1, have been identified as having an adverse prognostic relevance in B-cell chronic lymphocytic leukemia (B-CLL). Conventional cytogenetic studies have shown that TP53 deletion in B-CLL is associated predominantly with 17p loss resulting from complex chromosomal rearrangements. We performed genome-wide DNA (SNPs arrays), fluorescence in situ hybridization (FISH) and gene expression profiling (GEP) analyses to investigate the significance of 17p loss in a panel of 71 genetically well-characterized B-CLLs in Binet stage A, 18 of which carried a TP53 monoallelic deletion. Combined SNP arrays and FISH approaches showed 17p loss in all of the TP53-deleted cases, with breakpoints scattered along the 17p11.2 region. Mutations in exons 5 to 9 of TP53 were found in 9/12 deleted samples. GEP of 60 B-CLLs, including 7 patients with 17p loss, identified 40 differentially expressed genes in 17p- versus 17p normal samples, 35 of which were down-regulated in 17p- tumors. The majority (30/35) of these transcripts, including putative tumor suppressor genes, mapped to 17p. Overall, these data indicate that, beside TP53 deletion, the concomitant loss of 17p arm may contribute to the strong negative prognostic impact known to be associated with this lesion in B-CLL. Keywords: transcriptional analysis of B-CLL with 17p loss patients This series of microarray experiments contains the gene expression profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 60 newly diagnosed patients (Binet stage A). Peripheral blood mononuclear cells from B-CLL patients were isolated by Ficoll-Hypaque density-gradient centrifugation and the proportion of CD5/CD19/CD23 triple positive B cells in the suspension was determined by direct immunofluorescence performed using a FACS-sort flow cytometer with antibodies to: CD19 FITC/PE, CD23 PE and CD5 Cy-Chrome. If B-CLL cells were less than 90%, T cells, NK cells and monocytes were removed by negative selection using CD3, CD56, CD16, and CD14 monoclonal antibody treatment followed by magnetic beads. 3 micrograms of total RNA was processed and, in accordance with the manufacturer's protocols, 15 micrograms of fragmented biotin-labelled cRNA were hybridized on GeneChip Human Genome U133A Arrays (Affymetrix Inc.). The arrays were scanned using the GeneChip Scanner 3000 7G. The images were acquired using Affymetrix GeneChip® Operating Software (GCOS version 1.4) and the probe level data converted to expression values using the Bioconductor function for the Robust Multi-Array average (RMA) procedure (Irizarry et al, 2003), in which perfect match intensities are background adjusted and quantile-quantile normalised.
Experiment type
transcription profiling by array 
Contacts
Antonino Neri <emagene@policlinico.mi.it>, Daniela Intini, Fortunato Morabito, Gianluca Festini, Giorgio Lambertenghi-Deliliers, Giovanna Cutrona, Katia Todoerti, Laura Mosca, Luca Agnelli, Manlio Ferrarini, Marta Lionetti, Massimo Gentile, Massimo Spriano, Monica Colombo, Serena Matis, Sonia Fabris, Stefano Molica, Vincenzo Callea
Citation
Molecular and transcriptional characterization of 17p loss in B-cell chronic lymphocytic leukemia. Fabris S, Mosca L, Todoerti K, Cutrona G, Lionetti M, Intini D, Matis S, Colombo M, Agnelli L, Gentile M, Spriano M, Callea V, Festini G, Molica S, Lambertenghi Deliliers G, Morabito F, Ferrarini M, Neri A. , PMID:18521849
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-9992.idf.txt
Sample and data relationshipE-GEOD-9992.sdrf.txt
Raw data (1)E-GEOD-9992.raw.1.zip
Processed data (1)E-GEOD-9992.processed.1.zip
Array designA-AFFY-33.adf.txt
R ExpressionSetE-GEOD-9992.eSet.r
Links