Small regions of overlapping deletions on 6q26 in human astrocytic tumours identified using chromosome 6 tile path array-CGH.

Small regions of overlapping deletions on 6q26 in human astrocytic tumours identified using chromosome 6 tile path array-CGH.
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DOI:
10.1038/sj.onc.1209156
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发表时间:
2006-02-23
期刊:
影响因子:
8
通讯作者:
Collins, VP
Collins, VP
中科院分区:
医学1区
文献类型:
--
作者:
Ichimura, K;Mungall, AJ;Fiegler, H;Pearson, DM;Dunham, I;Carter, NP;Collins, VP

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6号染色体缺失是包括星形细胞肿瘤在内的多种人类恶性肿瘤中的常见异常,表明存在肿瘤抑制基因(TSG)。为了帮助识别候选TSGs,我们构建了6号染色体瓦片路径微阵列。该阵列包含1780个克隆(778个PAC和1002个BAC),覆盖了已发表的6号染色体序列的98.3%。使用该阵列分析了总共104例成人星形细胞肿瘤(10例弥漫性星形细胞瘤、30例间变性星形细胞瘤(AA)、64例胶质母细胞瘤(GB))。成功检测到单拷贝数变化,结果与微卫星分析基本一致。拷贝数变化的模式是复杂的,具有多个间质缺失/获得。然而,端粒6 q缺失占主导地位。两个小的共同和重叠区域的缺失在6 q26被确定。一个是1002 kb的大小,并包含PACRG和QKI,而第二个是199 kb,并拥有一个单一的基因,ARID 1B。数据显示,染色体6瓦片路径阵列可用于以高分辨率和准确度映射拷贝数变化。我们证实了AA和GB中6号染色体缺失的高频率,并确定了两个新的常见缺失区域,可能窝藏TSGs。
Deletions of chromosome 6 are a common abnormality in diverse human malignancies including astrocytic tumours, suggesting the presence of tumour suppressor genes (TSG). In order to help identify candidate TSGs, we have constructed a chromosome 6 tile path microarray. The array contains 1780 clones (778 PACs and 1002 BACs) that cover 98.3% of the published chromosome 6 sequences. A total of 104 adult astrocytic tumours (10 diffuse astrocytomas, 30 anaplastic astrocytomas (AA), 64 glioblastomas (GB)) were analysed using this array. Single copy number change was successfully detected and the result was in general concordant with a microsatellite analysis. The pattern of copy number change was complex with multiple interstitial deletions/gains. However, a predominance of telomeric 6q deletions was seen. Two small common and overlapping regions of deletion at 6q26 were identified. One was 1002 kb in size and contained PACRG and QKI, while the second was 199 kb and harbours a single gene, ARID1B. The data show that the chromosome 6 tile path array is useful in mapping copy number changes with high resolution and accuracy. We confirmed the high frequency of chromosome 6 deletions in AA and GB, and identified two novel commonly deleted regions that may harbour TSGs.
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