Dickinson John D, Joshi Avadhut, Iqbal Javeed, Sanger Warren, Bierman Philip J, Joshi Shantaram S
Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198-6395, USA.
Int J Mol Med. 2006 May;17(5):769-78.
This work describes the identification and impact of somatic genomic abnormalities in human chronic lymphocytic leukemia (CLL). Using molecular cytogenetics (FISH) and G-banding cytogenetic analysis, chromosome abnormalities were detected in 37 of 46 (80.4%) CLL patients. 13q14 deletion was the most common finding followed by trisomy 12 and 11q22.3 deletion. 17p13 deletion was also detected as were several less frequent chromosome abnormalities. The presence of these abnormalities significantly influenced the period of treatment-free survival as well as other clinical characteristics. In particular, CLL samples with trisomy 12 and 11q22.3 deletion were associated with shorter treatment-free survival. In order to identify the under-lying molecular differences among CLL subgroups with different chromosome abnormalities, gene expression profiling was performed on a custom DNA microarray consisting of 10,000 human gene-specific oligonucleotides. A gene dosage effect was observed where the expression of genes at the genetic loci of the sites of the somatic genomic abnormality was altered in a fashion according to the type of genomic change. This phenomenon was particularly evident in CLL samples with trisomy 12 and 17p13 deletion. Thus, this study demonstrates that genomic abnormalities influence gene expression in CLL by a dosage effect.
这项研究描述了人类慢性淋巴细胞白血病（CLL）中体细胞基因组异常的识别及其影响。通过分子细胞遗传学（FISH）和G带细胞遗传学分析，在46例CLL患者中的37例（80.4%）检测到染色体异常。13q14缺失是最常见的发现，其次是三体12和11q22.3缺失。还检测到17p13缺失以及其他一些不太常见的染色体异常。这些异常的存在显著影响了无治疗生存期以及其他临床特征。特别是，伴有三体12和11q22.3缺失的CLL样本与较短的无治疗生存期相关。为了确定具有不同染色体异常的CLL亚组之间潜在的分子差异，在由10,000个人类基因特异性寡核苷酸组成的定制DNA微阵列上进行了基因表达谱分析。观察到一种基因剂量效应，即体细胞基因组异常位点的基因座处的基因表达根据基因组变化的类型以一种方式改变。这种现象在伴有三体12和17p13缺失的CLL样本中尤为明显。因此，本研究表明基因组异常通过剂量效应影响CLL中的基因表达。
