High-resolution array CGH clarifies events occurring on 8p in carcinogenesis.
High-resolution array CGH clarifies events occurring on 8p in carcinogenesis.
复制标题
DOI：
10.1186/1471-2407-8-288
复制
发表时间：
2008-10-07
期刊：
影响因子：
3.8
通讯作者：
Edwards PA
中科院分区：
文献类型：
--
作者：
Cooke SL;Pole JC;Chin SF;Ellis IO;Caldas C;Edwards PA
8 号染色体短臂 (8p) 的重排在乳腺癌等上皮癌中非常常见。通常在 8p12 (29.7 Mb – 38.5 Mb) 中存在不平衡易位断点，并伴有远端 8p 丢失，有时伴有 8p11-12 的近端扩增。 8p11-12 中的重排已使用高分辨率阵列 CGH 进行了研究，但 8p 的前 30 Mb 的特征不太清楚，尽管该区域包含几个拟议的肿瘤抑制基因。我们通过阵列 CGH 以平铺路径 BAC 分辨率分析了 32 个乳腺癌细胞系和 6 个胰腺癌细胞系的整个 8p。使用区域 fosmid 阵列进一步表征了 8p12 远端的反复重排区域。对 60 多个乳腺肿瘤进行 FISH 和定量 RT-PCR 验证了原始材料中存在类似事件。我们确认 8p 通常丢失至少 30 Mb，但有几行显示该区域内的焦点丢失或拷贝数步骤。三个区域显示出至少两种情况共有的重排：两个反复丢失区域和一个扩增区域。在 6 个细胞系中发现 8p23.3 (0 Mb – 2.2 Mb) 范围内的丢失。在始终受影响的基因中，ARHGEF10 在 DU4475 细胞系中显示出剩余正常拷贝的点突变。 8p22 中 12.7 Mb – 19.1 Mb 范围内的删除，在两种情况下影响了 TUSC3。在 98 个肿瘤中的两个细胞系和一个肿瘤中的 8p21.3 (19.1 Mb – 23.4 Mb) 内发现了一种新的扩增子。 8p 上看到的重排模式可能是该染色体臂上潜在靶点高密度的结果，ARHGEF10 可能是一个新的候选抑癌基因。
Rearrangement of the short arm of chromosome 8 (8p) is very common in epithelial cancers such as breast cancer. Usually there is an unbalanced translocation breakpoint in 8p12 (29.7 Mb – 38.5 Mb) with loss of distal 8p, sometimes with proximal amplification of 8p11-12. Rearrangements in 8p11-12 have been investigated using high-resolution array CGH, but the first 30 Mb of 8p are less well characterised, although this region contains several proposed tumour suppressor genes. We analysed the whole of 8p by array CGH at tiling-path BAC resolution in 32 breast and six pancreatic cancer cell lines. Regions of recurrent rearrangement distal to 8p12 were further characterised, using regional fosmid arrays. FISH, and quantitative RT-PCR on over 60 breast tumours validated the existence of similar events in primary material. We confirmed that 8p is usually lost up to at least 30 Mb, but a few lines showed focal loss or copy number steps within this region. Three regions showed rearrangements common to at least two cases: two regions of recurrent loss and one region of amplification. Loss within 8p23.3 (0 Mb – 2.2 Mb) was found in six cell lines. Of the genes always affected, ARHGEF10 showed a point mutation of the remaining normal copies in the DU4475 cell line. Deletions within 12.7 Mb – 19.1 Mb in 8p22, in two cases, affected TUSC3. A novel amplicon was found within 8p21.3 (19.1 Mb – 23.4 Mb) in two lines and one of 98 tumours. The pattern of rearrangements seen on 8p may be a consequence of the high density of potential targets on this chromosome arm, and ARHGEF10 may be a new candidate tumour suppressor gene.
登录
查看更多内容
影响因子：
158.5
作者：
Falini, B;Mecucci, C;Martelli, MF
通讯作者：
Martelli, MF
影响因子：
3.7
作者：
Adélaïde, J;Huang, HE;Chaffanet, M
通讯作者：
Chaffanet, M
影响因子：
9.8
作者：
Hollox, EJ;Armour, JAL;Barber, JCK
通讯作者：
Barber, JCK
影响因子：
5.2
作者：
Gelsi-Boyer, W;Orsetti, B;Chaffanet, M
通讯作者：
Chaffanet, M
影响因子：
11.2
作者：
Heidenblad, M;Schoenmakers, EFPM;Höglund, M
通讯作者：
Höglund, M