Zatkova Andrea, Ullmann Reinhard, Rouillard Jean Marie, Lamb Barbara J, Kuick Rork, Hanash Sam M, Schnittger Susanne, Schoch Claudia, Fonatsch Christa, Wimmer Katharina
Institut für Medizinische Biologie, Universität Wien, Wien, Austria.
Genes Chromosomes Cancer. 2004 Apr;39(4):263-76. doi: 10.1002/gcc.20002.
Amplification within chromosome arm 11q involving the mixed-lineage leukemia gene (MLL) locus is a rare but recurrent aberration in acute myeloid leukemia and myelodysplastic syndrome (AML/MDS). We and others have observed that 11q amplifications in most AML/MDS cases have not been restricted to the chromosomal region surrounding the MLL gene. Therefore, we implemented a strategy to characterize comprehensively 11q amplicons in a series of 13 AML/MDS patients with MLL amplification. Analysis of 4 of the 13 cases by restriction landmark genomic scanning in combination with virtual genome scan and by matrix-based comparative genomic hybridization demonstrated that the 11q amplicon in these four cases consisted of at least three discontinuous sequences derived from different regions of the long arm of chromosome 11. We defined a maximally 700-kb sequence around the MLL gene that was amplified in all cases. Apart from the core MLL amplicon, we detected two additional 11q regions that were coamplified. Using fluorescence in situ hybridization (FISH) analysis, we demonstrated that sequences in 11q13.5 and 11q23-24 were amplified in 8 of 13 and 10 of 12 AML/MDS cases, respectively. Both regions harbor a number of potentially oncogenic genes. In all 13 cases, either one or both of these regions were coamplified with the MLL amplicon. Thus, we demonstrated that 11q amplicons in AML/MDS patients display a complex organization and have provided evidence for coamplification of two additional regions on the long arm of chromosome 11 that may harbor candidate target genes.
11号染色体长臂内涉及混合系白血病基因（MLL）位点的扩增在急性髓系白血病和骨髓增生异常综合征（AML/MDS）中是一种罕见但反复出现的畸变。我们和其他人已经观察到，大多数AML/MDS病例中的11q扩增并不局限于MLL基因周围的染色体区域。因此，我们实施了一项策略，对一系列13例伴有MLL扩增的AML/MDS患者的11q扩增子进行全面表征。通过限制性地标基因组扫描结合虚拟基因组扫描以及基于矩阵的比较基因组杂交对13例病例中的4例进行分析，结果表明这4例病例中的11q扩增子由至少三个来自11号染色体长臂不同区域的不连续序列组成。我们定义了一个围绕MLL基因的最大700 kb序列，该序列在所有病例中均被扩增。除了核心MLL扩增子外，我们还检测到另外两个共同扩增的11q区域。使用荧光原位杂交（FISH）分析，我们证明11q13.5和11q23 - 24区域的序列分别在13例AML/MDS病例中的8例和12例中的10例中被扩增。这两个区域都含有许多潜在的致癌基因。在所有13例病例中，这些区域中的一个或两个都与MLL扩增子共同扩增。因此，我们证明了AML/MDS患者中的11q扩增子呈现出复杂的结构，并为11号染色体长臂上另外两个可能含有候选靶基因的区域的共同扩增提供了证据。
