Transcription profiling of human granulocytes and CD3+ T lymphocytes from patients with Sazary syndrome
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: diego arcelli
PROVIDER: E-GEOD-17602 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This study used tumour and paired normal samples from 28 Sézary Syndrome (SS) patients to define recurrent regions of chromosomal aberrations. Our data identified recurrent losses of 17p13.2-p11.2 and 10p12.1-q26.3 occurring in 71 and 68% of cases respectively; common gains were detected for 17p11.2-q25.3 (64%) and chromosome 8/8q (50%). Moreover, we identified novel genomic lesions recurring in more than 30% of tumours: loss of 9q13-q21.33 and gain of 10p15.3-10p12.2. In the Sézary Syndrome cases analysed, we could find several small and few large Uniparental Disomies involving interstitial or telomeric regions of LOH occurring mainly for chromosome 10 and to a lesser extent for chromosome 9 and 17. In the attempt to correlate Copy Number data and clinical parameters we find a relationship between complex pattern of chromosomal aberrations, involving at least three recurrent Copy Number alterations, and shorter survival. Integrating mapping and transcriptional data we were able to identify a total of 113 deregulated transcripts in aberrant chromosomal regions that included cancer related genes such as members of the NF-kB pathway (BAG4, BTRC, NKIRAS2, PSMD3, TRAF2) that might explain its constitutive activation in CTCL. Matching this list of genes with those discriminating patients with different survival times we identify several common candidates that might exert critical roles in Sézary Syndrome, like BUB3 and PIP5K1B. Experiment Overall Design: Affymetrix Gene Expression arrays were performed, according to the manufacturer's directions, on RNA extracted from cryopreserved lymphomonocytes purified by Ficoll density gradient centrifugation and positive selection using anti-human CD3-conjugated dynabeads (tumour samples). Gene expression analyses of Affymetrix HG-U133 A arrays were performed for 32 tumour samples.
2009-10-10 | E-GEOD-17601 | biostudies-arrayexpress
Project description:This study used tumour and paired normal samples from 28 Sézary Syndrome (SS) patients to define recurrent regions of chromosomal aberrations. Our data identified recurrent losses of 17p13.2-p11.2 and 10p12.1-q26.3 occurring in 71 and 68% of cases respectively; common gains were detected for 17p11.2-q25.3 (64%) and chromosome 8/8q (50%). Moreover, we identified novel genomic lesions recurring in more than 30% of tumours: loss of 9q13-q21.33 and gain of 10p15.3-10p12.2. In the Sézary Syndrome cases analysed, we could find several small and few large Uniparental Disomies involving interstitial or telomeric regions of LOH occurring mainly for chromosome 10 and to a lesser extent for chromosome 9 and 17. In the attempt to correlate Copy Number data and clinical parameters we find a relationship between complex pattern of chromosomal aberrations, involving at least three recurrent Copy Number alterations, and shorter survival. Integrating mapping and transcriptional data we were able to identify a total of 113 deregulated transcripts in aberrant chromosomal regions that included cancer related genes such as members of the NF-kB pathway (BAG4, BTRC, NKIRAS2, PSMD3, TRAF2) that might explain its constitutive activation in CTCL. Matching this list of genes with those discriminating patients with different survival times we identify several common candidates that might exert critical roles in Sézary Syndrome, like BUB3 and PIP5K1B. Experiment Overall Design: Affymetrix SNP arrays were performed, according to the manufacturer's directions, on DNA extracted from cryopreserved lymphomonocytes purified by Ficoll density gradient centrifugation and positive selection using anti-human CD3-conjugated dynabeads (tumour samples) and from granulocytes (normal matched cells) obtained by collecting the upper phase overlying the Ficoll density gradient sediment. Copy number and LOH analyses of Affymetrix 10K SNP arrays were performed for 28 tumour samples and 28 matched normal samples used as references.
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Project description:The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the proto-oncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells following restoration of E2A expression, we identify a number of E2A-regulated genes that interfere with oncogenic signaling pathways including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity.
2011-07-07 | GSE21730 | GEO
Project description:The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the proto-oncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells following restoration of E2A expression, we identify a number of E2A-regulated genes that interfere with oncogenic signaling pathways including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity.
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