Affymetrix Gene Expression array data for Sézary Syndrome (SS) samples. Homo sapiens

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. 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.

本研究纳入28例塞扎里综合征（Sézary Syndrome, SS）患者的肿瘤样本及其配对正常样本，旨在明确染色体畸变的复发性区域。本研究数据显示，17p13.2-p11.2与10p12.1-q26.3区域的复发性缺失分别在71%和68%的病例中出现；而17p11.2-q25.3（64%）及8号染色体/8q（50%）区域则存在高频拷贝数扩增。此外，本研究还发现了在超过30%的肿瘤中反复出现的新型基因组病变：9q13-q21.33区域的缺失与10p15.3-10p12.2区域的扩增。在本次分析的塞扎里综合征病例中，我们观察到多处小型及少量大型单亲二体（Uniparental Disomy, UPD）事件，其涉及杂合性缺失（Loss of Heterozygosity, LOH）的间质区或端粒区，主要见于10号染色体，其次为9号与17号染色体。为探究拷贝数（Copy Number, CN）数据与临床参数的关联，本研究发现，携带至少3种复发性拷贝数变异的复杂染色体畸变模式与患者更短的总生存期相关。通过整合基因组定位与转录组数据，本研究在畸变染色体区域中共鉴定出113个失调转录本，其中包含与肿瘤相关的核因子κB（Nuclear Factor-kappa B, NF-κB）通路成员（如BAG4、BTRC、NKIRAS2、PSMD3、TRAF2），这些基因或可解释皮肤T细胞淋巴瘤（Cutaneous T-Cell Lymphoma, CTCL）中该通路的组成型激活现象。将该基因列表与区分不同生存期患者的基因集进行比对后，本研究鉴定出数个可能在塞扎里综合征中发挥关键作用的候选基因，例如BUB3与PIP5K1B。实验设计：本研究按照制造商说明书，对经菲科（Ficoll）密度梯度离心纯化并使用抗人CD3偶联戴诺磁珠（dynabeads）阳性分选的冻存淋巴单核细胞（肿瘤样本）提取的RNA，进行Affymetrix基因表达芯片检测。本研究针对32例肿瘤样本，采用Affymetrix HG-U133 A芯片完成基因表达分析。