Notable Losses at Specific Regions of Chromosomes 10q and 13q in the Sézary Syndrome Detected by Comparative Genomic Hybridization

Karenko, Leena; Kähkönen, Marketta; Hyytinen, E.; Lindlöf, Mikael; Ranki, Annamari

doi:10.1038/sj.jid.5600444

Cited by 56 publications

(71 citation statements)

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“…The DLG5 tumor suppressor gene, down-regulated in our Sezary syndrome samples, is located in 10q23, a chromosomal area often deleted in CTCL (10,40). In this study, we have for the first time correlated the chromosomal changes with aberrations observed in gene expression level in the same patient subset.…”

Section: Discussionmentioning

confidence: 81%

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Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma

Hahtola

Tuomela

Elo

et al. 2006

Clinical Cancer Research

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Purpose: Increased production of Th2 cytokines characterizes Sezary syndrome, the leukemic form of cutaneous T-cell lymphomas (CTCL). To identify the molecular background and to study whether shared by the most common CTCL subtype, mycosis fungoides, we analyzed the gene expression profiles in both subtypes. Experimental Design: Freshly isolated cells from 30 samples, representing skin, blood, and enriched CD4+ cell populations of mycosis fungoides and Sezary syndrome, were analyzed with Affymetrix (Santa Clara, CA) oligonucleotide microarrays, quantitative PCR, or immunohistochemistry. The gene expression profiles were combined with findings of comparative genomic hybridization of the same samples to identify chromosomal changes affecting the aberrant gene expression. Results: We identified a set of Th1-specific genes [e.g., TBX21 (T-bet), NKG7, and SCYA5 (RANTES)] to be down-regulated in Sezary syndrome as well as in a proportion of mycosis fungoides samples. In both Sezary syndrome and mycosis fungoides blood samples, the S100P and LIR9 gene expression was up-regulated. In lesional skin, IL7R and CD52 were up-regulated. Integration of comparative genomic hybridization and transcriptomic data identified chromosome arms 1q, 3p, 3q, 4q, 12q, 16p, and 16q as likely targets for new CTCL-associated gene aberrations. Conclusions: Our findings revealed several new genes involved in CTCL pathogenesis and potential therapeutic targets. Down-regulation of a set of genes involved in Th1 polarization, including the major Th1-polarizing factor, TBX21, was for the first time associated with CTCL. In addition, a plausible explanation for the proliferative response of CTCL cells to locally produced interleukin-7 was revealed.

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Section: Discussionmentioning

confidence: 81%

“…Previously, several studies on CTCL have pointed out chromosomal instability as a hallmark of the disease (10,39,43); thus, chromosomal aberrations may affect gene expression (11). The DLG5 tumor suppressor gene, down-regulated in our Sezary syndrome samples, is located in 10q23, a chromosomal area often deleted in CTCL (10,40).…”

Section: Discussionmentioning

confidence: 91%

Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma

Hahtola

Tuomela

Elo

et al. 2006

Clinical Cancer Research

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“…The SNP analysis for copy number determination identified three common regions of loss within 9q13-q21.33, 10p12.1-q26.3 and 17p13.2-p11.2, whereas copy number gain were defined for 8p23.3-q24.3, 10p15.3-p12.2, and 17p11.2-q25.3. These chromosomes have long been established to be among the mostly affected by cytogenetic aberrations in CTCL using conventional techniques (2,(26)(27)(28)(29)(30)(31). More recently, aCGH has been used by Vermeer and colleagues (3) in a genome-wide survey of 20 SS cases; their findings identified 17p13.1-p11.2 loss in 75% of cases, a complex pattern of deletions of chromosome 10 with eight discrete regions of highly recurrent loss (40-60%).…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Regions and Genes Important in the Pathogenesis of Sézary Syndrome by Combining Genomic and Expression Microarrays

et al. 2009

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In this study, we used single nucleotide polymorphism and comparative genomic hybridization array to study DNA copy number changes and loss of heterozygosity for 28 patients affected by Sézary syndrome (SS), a rare form of cutaneous Tcell lymphoma (CTCL). Our data identified, further confirming previous studies, 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 >30% of tumors: loss of 9q13-q21.33 and gain of 10p15.3-10p12.2. Individual chromosomal aberrations did not show a significant correlation with prognosis; however, when more than three recurrent chromosomal alterations (gain or loss) were considered, a statistical association was observed using Kaplan-Meier survival analysis. 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-κB pathway (BAG4, BTRC, NKIRAS2, PSMD3, and 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 SS, such as BUB3 and PIP5K1B. Altogether, our study confirms and maps more precisely the regions of gain and loss and, combined to transcriptional profiles, suggests a novel set of genes of potential interest in SS. [Cancer Res 2009;69(21):8438-46]

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“…86,87 Several studies have identified a consistent pattern of identical chromosomal abnormalities in SS, which was almost identical to that in MF, suggesting that both conditions represent parts of the same spectrum of disease with a similar pathogenesis. 88,89 Chromosomal amplification of the JUNB gene, a member of the activator protein-1 (AP-1) transcription factor complex involved in cell proliferation and T helper 2 (Th2) cytokine expression by T cells, has been identified in SS. 90,91 Prognosis and predictive factors.…”

Section: Sé Zary Syndromementioning

confidence: 99%

WHO-EORTC classification for cutaneous lymphomas

Willemze

Jaffe

Burg

et al. 2005

Blood

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4,355

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Notable Losses at Specific Regions of Chromosomes 10q and 13q in the Sézary Syndrome Detected by Comparative Genomic Hybridization

Cited by 56 publications

References 0 publications

Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma

Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma

Identification of Key Regions and Genes Important in the Pathogenesis of Sézary Syndrome by Combining Genomic and Expression Microarrays

WHO-EORTC classification for cutaneous lymphomas

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