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E-GEOD-57942 - aCGH data of 5 cases of Hepatosplenic T-cell lymphoma

Status
Released on 24 May 2014, last updated on 3 June 2014
Organism
Homo sapiens
Samples (10)
Array (1)
Protocols (8)
Description
Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma cytogenetically characterized by isochromosome 7q [i(7)(q10)], of which the molecular consequences remain unknown. We report here results of an integrative genomic and transcriptomic (expression microarray and RNA-sequencing) study of six HSTL cases with i(7)(q10) and three cases with ring 7 [r(7)], a rare variant aberration. Using high resolution array CGH, we prove that HSTL is characterized by the common loss of a 34.88 Mb region at 7p22.1p14.1 (3506316-38406226 bp) and duplication/amplification of a 38.77 Mb region at 7q22.11q31.1 (86259620-124892276 bp). Our data indicate that i(7)(q10)/r(7)-associated loss of 7p22.1p14.1 is a critical event in the development of HSTL, while gain of 7q sequences drives progression of the disease and underlies its intrinsic chemoresistance. Loss of 7p22.1p14.1 does not target a postulated tumor suppressor gene but unexpectedly enhances the expression of CHN2 from the remaining 7p allele, resulting in overexpression of β2-chimerin and dysregulation of a pathway involving RAC1 and NFATC2 with a cell proliferation response. Gain of 7q leads to increased expression of critical genes, including RUNDC3B, PPP1R9A and ABCB1, a known multidrug resistance gene. RNA-sequencing did not identify any additional recurrent mutations or gene fusions, suggesting that i(7)(q10) is the only driver event in this tumor. Our study confirms the previously described gene expression profile of HSTL and identifies a set of 24 genes, including three located on chromosome 7 (CHN2, ABCB1 and PPP1R9A), distinguishing HSTL from other malignancies Total genomic DNA was isolated from fresh frozen lymphoma samples using standard procedures. Genomic profiling, following the manufacturer’s protocols, was performed using the Agilent 244k (www.agilent.com) (5 cases)
Experiment type
comparative genomic hybridization by array 
Contacts
Julio Finalet <julio.finaletferreiro@med.kuleuven.be>, Anne Uyttebroeck, Gregor Verhoef, Helena Urbankova, Iwona Wlodarska, Jan Cools, Jo-Anne van der Krogt, Julio F Ferreiro, Laszlo Krenacs, Leila Rouhigharabaei, Lucienne Michaux, Pascale De Paepe, Peter Vandenberghe, Shashirekha Shetty, Thomas Tousseyn, Tom Taghon
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-57942.idf.txt
Sample and data relationshipE-GEOD-57942.sdrf.txt
Raw data (2)E-GEOD-57942.raw.1.zip, E-GEOD-57942.raw.2.zip
Processed data (1)E-GEOD-57942.processed.1.zip
Array designA-GEOD-9128.adf.txt
Links