Gains and overexpression identify DEK and E2F3 as targets of chromosome 6p gains in retinoblastoma
Gains and overexpression identify DEK and E2F3 as targets of chromosome 6p gains in retinoblastoma
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DOI：
10.1038/sj.onc.1208792
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发表时间：
2005-09-22
期刊：
影响因子：
8
通讯作者：
Lohmann, DR
中科院分区：
文献类型：
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作者：
Grasemann, C;Gratias, S;Lohmann, DR
儿童眼肿瘤视网膜母细胞瘤是由染色体13 q上的肿瘤抑制因子RB 1失活引起的。除了RB 1缺失外，许多视网膜母细胞瘤还显示其他遗传改变，包括染色体6p 21-pter和1 q31-q32上的增益。最近，6号染色体上的最小增益区域被缩小到p22带。我们研究了原发性视网膜母细胞瘤的基因组增益和表达变化，以确定6p 22中的潜在靶基因。定量多重PCR在25个（33%）肿瘤中检测到拷贝数>= 3，并且在76个肿瘤中的31个（40%）肿瘤中没有增加。其余20个（26%）样本仅在某些位点显示增益，最常见的包括6p22.3中的E2 F3和DEK。对21例原发性视网膜母细胞瘤的RNA分析表明，6p 22中这些基因和其他一些基因的表达水平与DNA获得相对应。然而，KIF 13 A，一个报告的候选癌基因在6p，表达水平低或不存在。在所有6p 22基因座的增益肿瘤的临床表现是不同的，在诊断时的年龄分布显着转移到年龄较大的肿瘤相比，没有或部分增益。总之，我们的研究结果表明，DEK和E2 F3是视网膜母细胞瘤中6p增益的潜在靶点。
The paediatric eye tumour retinoblastoma is initiated by inactivation of RB1, a tumour suppressor on chromosome 13q. In addition to RB1 loss, many retinoblastomas show other genetic alterations including gains on chromosomes 6p21-pter and 1q31-q32. Recently, the minimal region of gains on chromosome 6 was narrowed to band p22. We examined genomic gains and expression changes in primary retinoblastomas to identify potential target genes in 6p22. Quantitative multiplex PCR detected copy numbers >= 3 in 25 (33%) tumours and no gains in 31 of 76 (40%) tumours. The remaining 20 (26%) samples showed gains only at some loci, most often including E2F3 and DEK in 6p22.3. Analysis of RNA from 21 primary retinoblastomas showed that expression levels of these and some other genes in 6p22 correspond to DNA gains. However, KIF 13A, a reported candidate oncogene on 6p, was expressed at low levels or absent. Clinical manifestation of tumours with gains at all 6p22 loci was distinct in that distribution of age at diagnosis was markedly shifted to older age compared to tumours with no or partial gains. In summary, our results suggest that DEK and E2F3 are potential targets of 6p gains in retinoblastoma.