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

机译:使用染色体6切片路径阵列CGH鉴定的人类星形细胞肿瘤中6q26重叠缺失的小区域

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摘要

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.
机译:6号染色体的缺失是包括恶性肿瘤在内的各种人类恶性肿瘤的常见异常现象,提示存在抑癌基因(TSG)。为了帮助识别候选TSG,我们构建了6号染色体平铺路径微阵列。该阵列包含1780个克隆(778个PAC和1002个BAC),覆盖98.3%的已发布6号染色体序列。使用该阵列分析了总共104个成人星形细胞肿瘤(10个弥漫性星形细胞瘤,30个间变性星形细胞瘤(AA),64个胶质母细胞瘤(GB))。成功检测到单拷贝数变化,其结果与微卫星分析基本一致。复制数量变化的模式很复杂,存在多个插页删除/增加。然而,端粒6q删除占主导地位。在6q26处鉴定出两个小的共同缺失区域和重叠区域。一个是1002 kb,包含PACRG和QKI,第二个是199 kb,具有一个单一基因ARID1B。数据表明,第6号染色体图块路径阵列可用于以高分辨率和准确性映射副本数变化。我们确认了AA和GB中6号染色体缺失的高频率,并确定了可能包含TSG的两个新的常见缺失区域。

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