Comment[ArrayExpressAccession] E-GEOD-57942 MAGE-TAB Version 1.1 Public Release Date 2014-05-24 Investigation Title aCGH data of 5 cases of Hepatosplenic T-cell lymphoma Comment[Submitted Name] aCGH data of 5 cases of Hepatosplenic T-cell lymphoma Experiment 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) Term Source Name ArrayExpress EFO Term Source File http://www.ebi.ac.uk/arrayexpress/ http://www.ebi.ac.uk/efo/efo.owl Person Last Name Finalet Ferreiro Rouhigharabaei Urbankova van der Krogt Michaux Shetty Krenacs Tousseyn De Paepe Uyttebroeck Verhoef Taghon Vandenberghe Cools Wlodarska Person First Name Julio Julio Leila Helena Jo-Anne Lucienne Shashirekha Laszlo Thomas Pascale Anne Gregor Tom Peter Jan Iwona Person Mid Initials F Person Email julio.finaletferreiro@med.kuleuven.be Person Affiliation KULeuven Person Address KULeuven, Herestraat 49, Leuven, Belgium Person Roles submitter Protocol Name P-GSE57942-1 P-GSE57942-5 P-GSE57942-6 P-GSE57942-2 P-GSE57942-3 P-GSE57942-4 P-GSE57942-7 Protocol Description Agilent Feature Extraction Software (v 9.1.1) was used for background subtraction and LOWESS normalization. ID_REF = VALUE = Lowess Log2 ratio ch1/ch2 Agilent lable protocol Oligoarray control targets and hybridization buffer (Agilent In Situ Hybridization Kit Plus) were added, and samples were applied to microarrays enclosed in Agilent SureHyb-enabled hybridization chambers. After hybridization, slides were washed sequential no treatment natural tumor standard DNA extraction protocol Agilent Scanner protocol for a full slide Protocol Type normalization data transformation protocol labelling protocol hybridization protocol sample treatment protocol growth protocol nucleic acid extraction protocol array scanning protocol Experimental Factor Name KARYOTYPE Experimental Factor Type karyotype Comment[SecondaryAccession] GSE57942 Comment[GEOReleaseDate] 2014-05-24 Comment[ArrayExpressSubmissionDate] 2014-05-23 Comment[GEOLastUpdateDate] 2014-05-24 Comment[AEExperimentType] comparative genomic hybridization by array SDRF File E-GEOD-57942.sdrf.txt