Transcriptomics

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Identification of a tumor suppressor network in T-cell leukemia.


ABSTRACT: In T-cell acute lymphoid leukemia (T-ALL) several oncogenes and tumour suppressor (TS) genes have been described. Deregulation of these genes mostly results from genomic aberrations, including translocations, amplifications and deletions. To identify novel cancer-related genes targeted by copy number alterations we performed genomic profiling of eight T-ALL cell lines. In three of these (HPB-ALL, JURKAT, MOLT-14) we identified a shared deletion at chromosomal position 2p16.3-p21. Within the minimally deleted region we recognized several candidate TS genes, including FBXO11 (component of the ubiquitin-pathway) and FOXN2 (developmental transcription factor). Furthermore, an additional deletion at 14q23.2-q32.11 (in cell line RPMI-8402) included FOXN3, highlighting this class of FOX genes as potential TS. Accordingly, quantitative expression analyses of FBXO11, FOXN2 and FOXN3 confirmed reduced transcript levels in the indicated cell lines. Moreover, reduced expression of these genes was also observed in about 7 % of T-ALL patients from a public dataset (GSE26713), showing their clinical relevance in this malignancy. Bioinformatic analyses of these patient data revealed concurrent reduction of FOXN2 and/or FOXN3 together with homeobox gene ZHX1. Consistently, knockdown experiments and reporter gene assays demonstrated that both FOXN2 and FOXN3 directly activated transcription of ZHX1 in T-ALL. ZHX1 target gene analysis via expression profiling after siRNA-mediated knockdown indicated regulation of several genes involved in the ubiquitin-pathway including CUL4A. Taken together, we identified novel TS genes which form a regulatory network improving our understanding of T-cell development and leukemogenesis.

ORGANISM(S): Homo sapiens  

DISEASE(S): Acute Lymphoblastic Leukemia

SUBMITTER: Claudia Pommerenke  

PROVIDER: E-MTAB-5232 | ArrayExpress | 2017-02-01

REPOSITORIES: ArrayExpress

Dataset's files

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E-MTAB-5232.idf.txt Idf
E-MTAB-5232.raw.1.zip Raw
E-MTAB-5232.raw.2.zip Raw
E-MTAB-5232.sdrf.txt Txt
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Publications

Identification of a tumor suppressor network in T-cell leukemia.

Nagel Stefan S   Pommerenke Claudia C   Meyer Corinna C   Kaufmann Maren M   MacLeod Roderick A F RAF   Drexler Hans G HG  

Leukemia & lymphoma 20170131 9


To identify novel cancer-related genes targeted by copy number alterations, we performed genomic profiling of T-cell acute lymphoblastic leukemia (T-ALL) cell lines. In 3/8, we identified a shared deletion at chromosomal position 2p16.3-p21. Within the minimally deleted region, we recognized several candidate tumor suppressor (TS) genes, including FBXO11 and FOXN2. An additional deletion at chromosome 14q23.2-q32.11 included FOXN3, highlighting this class of FOX genes as potential TS. Quantitati  ...[more]

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