Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma
Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma
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DOI：
10.1182/blood-2010-07-297861
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发表时间：
2011-01-27
期刊：
影响因子：
20.3
通讯作者：
Ko, Young-Hyeh
中科院分区：
文献类型：
--
作者：
Sung, Chang Ohk;Kim, Sang Cheol;Ko, Young-Hyeh
在原发性中枢神经系统淋巴瘤(PCNSL)的遗传变化中，人们知之甚少。为了检测PCNSL中拷贝数的改变和差异表达基因，我们用基于高分辨率阵列的比较基因组杂交技术分析了总共12个PCNSL样本，并在12个样本中的7个样本中进行了表达谱分析。最常见的缺失有8例(66.7%)发生在含有CDKN2A的9p21.3。我们汇编了前96个基因(家族错误率，P<；0.05)，显示了PCNSL和正常淋巴结组织之间最大的差异表达。从中我们选择了8个候选基因(NPFFR2、C4orf7、OSMR、EMCN、TPO、FNDC1、COL12A1和MSC)，它们的表达变化与拷贝数异常有关。所有8个基因在微阵列中表达下调，在基于阵列的比较基因组杂交分析中显示缺失。这些基因参与细胞信号传递或细胞黏附。此外，C4orf7基因低表达与生存不良显著相关(P=.0425)。通过基因集浓缩分析，我们发现了一些可能参与PCNSL发病的信号转导途径，如Janus激酶信号转导和转录激活因子通路以及黏附相关通路。总之，这项研究确定了新的肿瘤抑制基因，可能作为PCNSL的治疗靶点。(血。2011；117(4)：1291-1300)
Of the genetic changes in primary central nervous system lymphoma (PCNSL), little is known. To detect copy number alterations and differentially expressed genes in PCNSL, we analyzed a total of 12 PCNSL samples with high-resolution array-based comparative genomic hybridization and performed expression profiling in 7 of the 12 samples. The most frequent deletion found in 8 patients (66.7%) occurred in 9p21.3 containing CDKN2A. We compiled the top 96 genes (family-wise error rate, P < .05) showing the greatest differential expression between PCNSL and normal lymph node tissues. From these, we selected 8 candidate genes (NPFFR2, C4orf7, OSMR, EMCN, TPO, FNDC1, COL12A1, and MSC) in which expression changes were associated with copy number aberrations. All 8 genes showed both down-regulation in expression microarray and deletion in array-based comparative genomic hybridization analyses. These genes participate in cell signaling or cell adhesion. In addition, low mRNA expression of C4orf7 was significantly associated with poor survival (P = .0425). Using gene set enrichment analysis, we identified several signal transduction pathways, such as Janus kinase-signal transducers and activators of transcription pathway and adhesion-related pathways, which may be involved in pathogenesis of PCNSL. In conclusion, this study identified novel tumor suppressor genes that may serve as therapeutic targets of PCNSL. (Blood. 2011; 117(4): 1291-1300)