Transcriptomics

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ACGH data of 5 cases of Hepatosplenic T-cell lymphoma


ABSTRACT: 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)

ORGANISM(S): Homo sapiens  

SUBMITTER: Leila Rouhigharabaei   Lucienne Michaux  Helena Urbankova  Jan Cools  Iwona Wlodarska  Anne Uyttebroeck  Gregor Verhoef  Tom Taghon  Jo-Anne van der Krogt  Laszlo Krenacs  Julio Finalet  Julio F Ferreiro  Shashirekha Shetty  Thomas Tousseyn  Pascale De Paepe  Peter Vandenberghe 

PROVIDER: E-GEOD-57942 | ArrayExpress | 2014-05-24

SECONDARY ACCESSION(S): GSE57942PRJNA248464

REPOSITORIES: GEO, ArrayExpress

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