Comprehensive profiling of 8p11-12 amplification in breast cancer
Comprehensive profiling of 8p11-12 amplification in breast cancer
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DOI：
10.1158/1541-7786.mcr-05-0128
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发表时间：
2005-12-01
影响因子：
5.2
通讯作者：
Chaffanet, M
中科院分区：
文献类型：
--
作者：
Gelsi-Boyer, W;Orsetti, B;Chaffanet, M
在人类癌，尤其是乳腺癌中，染色体ARM 8P经常参与复杂的染色体重排，这些重排在8p11-12时结合了放大，在8p12-21区域中断和8p21-ter的损失。几项研究已经确定了8p11-12扩增子中的推定致癌基因。但是，差异和对这种扩增结构的知识的缺乏使我们认为肿瘤基因的实际认同不是确定的。我们在这里提出了一项综合研究，结合了乳腺细胞系和原发性乳腺肿瘤中8p11-12区域的基因组，表达和染色体断裂分析。我们使用阵列比较基因组杂交在8p11-12处显示了四个扩增子的存在。使用DNA微阵列对123个样品的基因表达分析鉴定出与扩增相关的14个基因。使用在组织微阵列上的荧光原位杂交分析，我们显示了一群跨越端粒至扩增相关的区域的断点群的存在。最后，我们表明8P11-12扩增对乳腺癌的生存有贬义。
In human carcinomas, especially breast cancer, chromosome arm 8p is frequently involved in complex chromosomal rearrangements that combine amplification at 8p11-12, break in the 8p12-21 region, and loss of 8p21-ter. Several studies have identified putative oncogenes in the 8p11-12 amplicon. However, discrepancies and the lack of knowledge on the structure of this amplification lead us to think that the actual identity of the oncogenes is not definitively established. We present here a comprehensive study combining genomic, expression, and chromosome break analyses of the 8p11-12 region in breast cell lines and primary breast tumors. We show the existence of four amplicons at 8p11-12 using array comparative genomic hybridization. Gene expression analysis of 123 samples using DNA microarrays identified 14 genes significantly overexpressed in relation to amplification. Using fluorescence in situ hybridization analysis on tissue microarrays, we show the existence of a cluster of breakpoints spanning a region just telomeric to and associated with the amplification. Finally, we show that 8p11-12 amplification has a pejorative effect on survival in breast cancer.