Identification of candidate tumour suppressor gene loci for Hodgkin and Reed-Sternberg cells by characterisation of homozygous deletions in classical Hodgkin lymphoma cell lines
Identification of candidate tumour suppressor gene loci for Hodgkin and Reed-Sternberg cells by characterisation of homozygous deletions in classical Hodgkin lymphoma cell lines
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DOI：
10.1111/j.1365-2141.2008.07262.x
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发表时间：
2008-09-01
影响因子：
6.5
通讯作者：
Siebert, Reiner
中科院分区：
文献类型：
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作者：
Giefing, Maciej;Arnemann, Joachim;Siebert, Reiner
几个肿瘤抑制基因（TSG）已被确定为在癌细胞中定位纯合缺失的结果。为了确定典型霍奇金淋巴瘤（cHL）发病机制中可能涉及的TSG，我们使用四种不同的阵列比较基因组杂交（array-CGH）平台研究了四种cHL细胞系（L428，HDLM 2，KMH 2，L1236），并专注于高分辨率鉴定纯合缺失。在79个双等位基因缺失的候选区域中，除了先前描述的区域外，还可以通过聚合酶链反应验证28个新的纯合缺失区域。这些区域的大小从13 kb到619 kb不等。28个新的双等位基因丢失中有11个是推定的拷贝数多态性。这留下了17个区域，可能窝藏新的肿瘤抑制因子参与霍奇金淋巴瘤。用两种不同平台的表达谱分析证实了位于纯合缺失中的大多数基因缺乏表达。此外，位于同源性缺失区域的基因的本体论注释的分析表明参与细胞凋亡和细胞死亡的基因的富集。总之，通过定位细胞系中的纯合缺失，本研究鉴定了一系列基因，如SEPT 9、GNG 7和CYBB，它们可能编码参与cHL发病机制的候选肿瘤抑制因子。
Several tumour suppressor genes (TSG) have been identified as a result of mapping homozygous deletions in cancer cells. To identify putative TSG involved in the pathogenesis of classical Hodgkin lymphoma (cHL), we investigated four cHL cell lines (L428, HDLM2, KMH2, L1236) using four different array-Comparative Genomic Hybridisation (array-CGH) platforms and focused on high resolution identification of homozygous deletions. Out of 79 candidate regions of bi-allelic loss identified by array-CGH, besides previously described regions, 28 novel regions of homozygous deletions could be verified by polymerase chain reaction. These regions ranged from 13 kb to 619 kb in size. Eleven of the 28 novel bi-allelic losses were putative copy number polymorphisms. This left 17 regions that might harbour novel tumour suppressors involved in Hodgkin lymphoma. Expression profiling with two different platforms confirmed lack of expression of the majority of the genes located in the homozygous deletions. Furthermore, analysis of ontology annotations of genes located in the homozygously deleted regions indicated an enrichment of genes involved in apoptosis and cell death. In summary, through the mapping of homozygous deletions in cell lines this study identified a series of genes, such as SEPT9, GNG7 and CYBB, which might encode candidate tumour suppressors involved in the pathogenesis of cHL.