Amplification of a 280-kilobase core region at the ERBB2 locus leads to activation of two hypothetical proteins in breast cancer
Amplification of a 280-kilobase core region at the ERBB2 locus leads to activation of two hypothetical proteins in breast cancer
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DOI：
10.1016/s0002-9440(10)63556-0
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发表时间：
2003-11-01
影响因子：
6
通讯作者：
Kallioniemi, A
中科院分区：
文献类型：
--
作者：
Kauraniemi, P;Kuukasjärvi, T;Kallioniemi, A
在17季度，ERBB2癌基因在临床上是乳腺癌中最相关的遗传畸变，而多项研究将ERBB2激活与临床不良结局联系起来。基于ERBB2过表达肿瘤的靶向抗体治疗的发展以及ER-BB2作为化学疗法治疗反应的预测因子的可能作用进一步强调了ERBB2在乳腺癌中的重要作用。在这里，我们对原发性乳腺肿瘤中ERBB2扩增子发生的分子事件进行了详细的表征。通过与组织微阵列的荧光原位杂交对330个乳腺肿瘤中扩增子结构的分析显示，一个280 kb的扩增区域包含10个转录序列，包括八个已知基因。通过使用定量的实时逆转录酶 - 促酶 - 促酶链反应反应，在36个冷冻匹配的ER-BB2放大和非置型（通过荧光原位杂交）原发性乳腺肿瘤的冷冻样品中确定了这10个转录本的表达水平。对于其中六个基因，包括ERBB2和两个未表征的假设蛋白MGC9753和MGC14832观察到了扩增和表达水平之间的高度显着关联。这些结果支持了有关拷贝数对基因表达水平的影响的最新发现，并突出了可能有助于ERBB2放大乳腺肿瘤的临床行为的新型基因。
Amplification of the ERBB2 oncogene at 17q12 is clinically the most relevant genetic aberration in breast cancer and several studies have linked ERBB2 activation to poor clinical outcome. The development of targeted antibody-based therapy for ERBB2-overexpressing tumors and the possible role of ER-BB2 as a predictor of chemotherapy treatment response have further emphasized the essential role of ERBB2 in breast cancer. Here, we performed a detailed characterization of the molecular events occurring at the ERBB2 amplicon in primary breast tumors. Analysis of the amplicon structure in 330 breast tumors by fluorescence in situ hybridization to a tissue microarray revealed a 280-kb common region of amplification that contains 10 transcribed sequences, including eight known genes. The expression levels of these 10 transcripts were determined in 36 frozen samples of grade-matched ER-BB2-amplified and -nonamplifled (as determined by fluorescence in situ hybridization) primary breast tumors by using quantitative real-time reverse transcriptase-polymerase chain reaction. A highly significant association between amplification and expression levels was observed for six of these genes, including ERBB2 and two uncharacterized hypothetical proteins, MGC9753 and MGC14832. These results support the recent findings on the influence of copy number on gene expression levels and highlight novel genes that might contribute to the clinical behavior of ERBB2-amplified breast tumors.