Bredel Markus, Bredel Claudia, Juric Dejan, Harsh Griffith R, Vogel Hannes, Recht Lawrence D, Sikic Branimir I
Division of Oncology, Center for Clinical Sciences Research, Stanford University School of Medicine, Stanford, California 94305-5151, USA.
Cancer Res. 2005 May 15;65(10):4088-96. doi: 10.1158/0008-5472.CAN-04-4229.
High-resolution genome-wide mapping of exact boundaries of chromosomal alterations should facilitate the localization and identification of genes involved in gliomagenesis and may characterize genetic subgroups of glial brain tumors. We have done such mapping using cDNA microarray-based comparative genomic hybridization technology to profile copy number alterations across 42,000 mapped human cDNA clones, in a series of 54 gliomas of varying histogenesis and tumor grade. This gene-by-gene approach permitted the precise sizing of critical amplicons and deletions and the detection of multiple new genetic aberrations. It has also revealed recurrent patterns of occurrence of distinct chromosomal aberrations as well as their interrelationships and showed that gliomas can be clustered into distinct genetic subgroups. A subset of detected alterations was shown predominantly associated with either astrocytic or oligodendrocytic tumor phenotype. Finally, five novel minimally deleted regions were identified in a subset of tumors, containing putative candidate tumor suppressor genes (TOPORS, FANCG, RAD51, TP53BP1, and BIK) that could have a role in gliomagenesis.
对染色体改变的确切边界进行全基因组高分辨率定位，应有助于定位和鉴定参与胶质瘤发生的基因，并可能对胶质脑肿瘤的遗传亚组进行特征描述。我们使用基于cDNA微阵列的比较基因组杂交技术进行了这样的定位，以分析一系列54例组织发生和肿瘤分级各异的胶质瘤中42,000个已定位人类cDNA克隆的拷贝数改变。这种逐个基因的方法能够精确确定关键扩增子和缺失的大小，并检测到多个新的基因畸变。它还揭示了不同染色体畸变的复发模式及其相互关系，并表明胶质瘤可聚类为不同的遗传亚组。检测到的一部分改变主要与星形细胞瘤或少突胶质细胞瘤的肿瘤表型相关。最后，在一部分肿瘤中鉴定出五个新的最小缺失区域，其中包含可能在胶质瘤发生中起作用的假定候选肿瘤抑制基因（TOPORS、FANCG、RAD51、TP53BP1和BIK）。
