Zatkova Andrea, Schoch Claudia, Speleman Frank, Poppe Bruce, Mannhalter Christine, Fonatsch Christa, Wimmer Katharina
Abteilung für Humangenetik, Klinisches Institut für Medizinische und Chemische Labor Diagnostik (KIMCL), Medizinische Universität Wien, Währinger Strasse 10, A-1090 Vienna, Austria.
Genes Chromosomes Cancer. 2006 Sep;45(9):798-807. doi: 10.1002/gcc.20344.
Chromosome arm 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are rare but recurrent aberrations in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We have recently shown that in addition to the MLL core amplicon, independent sequences in 11q23-24 and/or 11q13.5 are coamplified within the same cytogenetic markers in 90% and 60% of patients, respectively. Here we further narrow down the minimal amplicon in 11q13.5 to 1.17 Mb by means of semi-quantitative PCR and FISH analyses. The newly defined amplicon contains seven genes, including the GRB2-associated binding protein 2 (GAB2). Using real-time RT-PCR we show a significant transcriptional upregulation of GAB2 in the patients who have GAB2 coamplified with MLL. Thus, the adaptor molecule GAB2 that has already been shown to enhance oncogenic signaling in other neoplasias appears as a novel target of 11q amplification in AML/MDS.
涉及混合谱系白血病基因（MLL）位点的11号染色体长臂扩增在急性髓系白血病（AML）和骨髓增生异常综合征（MDS）中罕见但反复出现。我们最近发现，除了MLL核心扩增子外，11q23 - 24和/或11q13.5中的独立序列分别在90%和60%的患者中与相同的细胞遗传学标记共同扩增。在此，我们通过半定量PCR和FISH分析进一步将11q13.5中的最小扩增子缩小至1.17 Mb。新定义的扩增子包含7个基因，包括GRB2相关结合蛋白2（GAB2）。使用实时RT-PCR，我们发现在GAB2与MLL共同扩增的患者中，GAB2转录显著上调。因此，已被证明在其他肿瘤中增强致癌信号的衔接分子GAB2似乎是AML/MDS中11号染色体扩增的一个新靶点。
