Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis.
Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis.
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DOI：
10.1038/onc.2009.34
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发表时间：
2009-04-30
期刊：
影响因子：
8
通讯作者：
Albertson, D. G.
中科院分区：
文献类型：
--
作者：
Kwek, S. S.;Roy, R.;Zhou, H.;Climent, J.;Martinez-Climent, J. A.;Fridlyand, J.;Albertson, D. G.
染色体8p11-8p12和11q12-11q14上的共扩张经常发生在乳腺肿瘤中，这表明在肿瘤发生中，基因之间可能合作。我们使用高分辨率阵列比较基因组杂交（阵列CGH）来绘制最小的扩增区域。 8p和11q扩增子很复杂，每个位置至少由四个扩增子核组成。通过组合拷贝数，RNA和蛋白质表达分析来鉴定候选癌基因映射到这些区域。这些研究还表明，在11q13处的CCND1诱导了8p12时ZnF703映射的表达，随后证明是通过RB/E2F途径介导的。进一步评估了来自8p12的9个候选癌基因，从11q13的第11季度进行了致癌功能的进一步评估。没有一个基因单独促进软琼脂中的菌落形成或在功能上彼此合作。另一方面，在8p12处的FGFR1和DDHD2与MYC合作，而CCND1和ZNF703与TP53的主要负面形式合作。这些观察结果突出了这些乳腺癌扩增子中发生的基因组重排的复杂性和功能后果，包括8p和11q扩增子基因之间的转录串扰，以及与肿瘤发生的主要途径的合作。
Co-amplification at chromosomes 8p11-8p12 and 11q12-11q14 occurs often in breast tumors, suggesting possible cooperation between genes in these regions in oncogenesis. We used high resolution array comparative genomic hybridization (array CGH) to map the minimal amplified regions. The 8p and 11q amplicons are complex and consist of at least four amplicon cores at each site. Candidate oncogenes mapping to these regions were identified by combining copy number and RNA and protein expression analyses. These studies also suggested that CCND1 at 11q13 induced expression of ZNF703 mapping at 8p12, which was subsequently shown to be mediated via the Rb/E2F pathway. Nine candidate oncogenes from 8p12 and four from 11q13 were further evaluated for oncogenic function. None of the genes individually promoted colony formation in soft agar or collaborated with each other functionally. On the other hand, FGFR1 and DDHD2 at 8p12 cooperated functionally with MYC, while CCND1 and ZNF703 cooperated with a dominant negative form of TP53. These observations highlight the complexity and functional consequences of the genomic rearrangements that occur in these breast cancer amplicons, including transcriptional cross-talk between genes in the 8p and 11q amplicons, as well as their cooperation with major pathways of tumorigenesis.
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DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
2.5
作者：
Ethier, Stephen P.
通讯作者：
Ethier, Stephen P.
影响因子：
11.2
作者：
Kan, Charlene E.;Patton, John T.;Jackson, Mark W.
通讯作者：
Jackson, Mark W.
影响因子：
50.3
作者：
Neve, Richard M.;Chin, Koei;Gray, Joe W.
通讯作者：
Gray, Joe W.
影响因子：
5.2
作者：
Gelsi-Boyer, W;Orsetti, B;Chaffanet, M
通讯作者：
Chaffanet, M