Characterization of target genes at the 2p15-16 amplicon in diffuse large B-cell lymphoma
Characterization of target genes at the 2p15-16 amplicon in diffuse large B-cell lymphoma
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DOI：
10.1111/j.1349-7006.2006.00209.x
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发表时间：
2006-06-01
期刊：
影响因子：
5.7
通讯作者：
Seto, Masao
中科院分区：
文献类型：
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作者：
Fukuhara, Noriko;Tagawa, Hiroyuki;Seto, Masao
在弥漫性大B细胞淋巴瘤（DLBCL）中观察到2 p扩增作为复发性改变。尽管两个候选癌基因，REL和BCL 11 A，已被研究作为2 p扩增的目标，问题仍然是扩增子中的真正的靶基因是REL，BCL 11 A还是两者兼而有之。我们先前通过全基因组阵列比较基因组杂交（CGH）在99例DLBCL病例中的25例中发现了染色体2 p的频繁基因组增益。所有这25例病例均包括2 p15 -16的复发性拷贝数增加。在这里介绍的研究中，通过重叠群细菌人工染色体（BAC）阵列CGH对2 p15 -16的4.5-Mb区域进行了更详细的分析，其中包含33个BAC克隆。我们将最小共同区域限制在500 kb的长度，其中只有候选癌基因REL，而不是BCL 11 A，位于。实时荧光定量PCR检测基因组获得量与表达量的相关性。结果显示两个基因具有显著相关性，表明这两个基因是2 p15 -16扩增子的共同靶标。然而，考虑到REL比BCL 11 A更频繁扩增的事实，REL基因可能在DLBCL的发病机制中发挥比BCL 11 A更重要的作用。
Amplification of 2p has been observed as a recurrent alteration in diffuse large B-cell lymphoma (DLBCL). Whereas two candidate oncogenes, REL and BCL11A, have been investigated as targets for 2p amplification, the question remains as to whether the true target gene in the amplicon is REL, BCL11A or both. We previously identified frequent genomic gains of chromosomal 2p in 25 out of 99 DLBCL cases by means of genome-wide array comparative genomic hybridization (CGH). All of these 25 cases included recurrent copy number gain at 2p15-16. In the study presented here, cases were analyzed in greater detail by means of contig bacterial artificial chromosome (BAC) array CGH for the 4.5-Mb region at 2p15-16, which contained 33 BAC clones. We confined the minimal common region to 500-kb in length, where only the candidate oncogene REL, and not BCL11A, is located. Real-time quantitative PCR was carried out to investigate the correlation between genomic gain and expression. It showed a significant correlation for both genes, indicating that these two genes are common targets for the 2p15-16 amplicon. However, given the fact that REL is more frequently amplified than BCL11A, the REL gene may play a more important role than BCL11A in the pathogenesis of DLBCL.