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| Status |
Public on Nov 11, 2008 |
| Title |
Molecular and transcriptional characterization of chromosome 17p loss in chronic lymphocytic leukemia, experiment B |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| Summary |
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: genomic analysis of B-CLL with 17p loss patients
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| Overall design |
This series of microarray experiments contains the genome-wide profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 12 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. 250 nanograms of genomic DNA was processed and, in accordance with the manufacturer's protocols, 40 micrograms of fragmented biotin-labelled DNA were hybridized on GeneChip Human Mapping 50K XbaI 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). Copy number values for individual SNPs were extracted and converted from CEL files into signal intensities using GTYPE 4.1 and Affymetrix Copy Number Analysis Tool (CNAT 4.0.1) softwares. Genomic Smoothing analysis was performed by using the smoothing window of 1 Mb, and inferred copy number states were derived from a Hidden Markov Model (HMM) based algorithm implemented in CNAT 4.0.1.
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| Contributor(s) |
Fabris S, Mosca L, Todoerti K, Cutrona G, Lionetti M, Intini D, Matis S, Colombo M, Agnelli L, Gentile M, Festini G, Callea V, Spriano M, Molica S, Lambertenghi-Deliliers G, Morabito F, Ferrarini M, Neri A |
| Citation(s) |
18521849 |
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| Submission date |
Apr 03, 2008 |
| Last update date |
Dec 22, 2017 |
| Contact name |
Luca Agnelli |
| E-mail(s) |
luca.agnelli@istitutotumori.mi.it, luca.agnelli@gmail.com
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| Phone |
+390223903581
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| Organization name |
IRCCS Istituto Nazionale dei Tumori
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| Department |
Department of Advanced Diagnostics
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| Street address |
Venezian 1
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| City |
MILAN |
| ZIP/Postal code |
20133 |
| Country |
Italy |
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| Platforms (1) |
| GPL2005 |
[Mapping50K_Xba240] Affymetrix Human Mapping 50K Xba240 SNP Array |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE11038 |
Molecular and transcriptional characterization of chromosome 17p loss in chronic lymphocytic leukemia |
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| Relations |
| BioProject |
PRJNA108809 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE11036_RAW.tar |
160.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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