E-TABM-702 - Transcription profiling by array of human non anaplastic T-cell lymphoma biopsies and cell lines

Status
Released on 31 December 2009, last updated on 23 July 2014
Organism
Homo sapiens
Samples (51)
Array (1)
Protocols (6)
Description
A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net) | Affymetrix HG-U133 Plus 2.0 : 7 NKTCL biopsies, 2 NKTCL cell lines (SNK6, SNT8), 16 PTCL NOS biopsies, 2 NK cells samples | Biopsies and cell lines of NK/T-cell lymphoma, nasal-type (NKTCL) were subject to combined gene expression profiling and array-based comparative genomic hybridization analyses. Compared to PTCL, NOS, NKTCL had higher transcript levels for NK-cell markers and cytotoxic molecules, especially granzyme H, a novel sensitive biomarker of NKTCL. Compared to normal NK cells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, EBV-induced genes and PDGFRA. Notably, PDGFR? and its phosphorylated form were confirmed at the protein level, and in vitro the MEC04 NKTCL-cell line was sensitive to imatinib. Deregulation of the AKT, JAKSTAT and NF-?B pathways suggested by bioinformatical analysis, was corroborated by nuclear expression of phosphorylated AKT, STAT3 and RelA in NKTCL, and several deregulated genes in these pathways mapped to regions of recurrent copy number aberrations (AKT3 (1q44), IL6R (1q21.3), CCL2 (17q12), TNFRSF21 (6p12.3)). Several features of NKTCL uncovered by this analysis (overexpression of VEGFA and its receptor KDR by the tumor cells, overexpression of MET-HGF) suggest deregulation of angiogenic pathways. Integrative analysis also identified a novel putative tumor suppressor HACE1 in the frequently deleted 6q21 region. This study highlights emerging oncogenic pathways in NKTCL and identifies novel diagnostic and therapeutic targets. | Submitter : Aurelien de Reynies <reyniesa@ligue-cancer.fr> | Project leader : Philippe Gaulard <philippe.gaulard@hmn.aphp.fr>
Experiment types
transcription profiling by array, cell type comparison, co-expression, disease state
Contact
Citation
Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type. Huang Y, de Reyniès A, de Leval L, Ghazi B, Martin-Garcia N, Travert M, Bosq J, Brière J, Petit B, Thomas E, Coppo P, Marafioti T, Emile JF, Delfau-Larue MH, Schmitt C, Gaulard P. Blood 115(6):1226-1237 (2010), Europe PMC 19965620
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-TABM-702.idf.txt
Sample and data relationshipE-TABM-702.sdrf.txt
Raw data (3)E-TABM-702.raw.1.zip, E-TABM-702.raw.2.zip, E-TABM-702.raw.3.zip
Processed data (1)E-TABM-702.processed.1.zip
Array designA-AFFY-44.adf.txt
Links