HER-2, TOP2A and chromosome 17 alterations in breast cancer
HER-2, TOP2A and chromosome 17 alterations in breast cancer
复制标题
DOI：
10.1007/bf02893497
复制
发表时间：
2007-01-01
影响因子：
2.8
通讯作者：
Dalay, Nejat
中科院分区：
文献类型：
--
作者：
Beser, Ash Rehber;Tuzlali, Sitki;Dalay, Nejat
HER-2扩增是识别对曲妥珠单抗有反应的患者的生物标志物，并已被评估为预测对蒽环类药物反应的因素。HER-2与蒽环类药物治疗反应的关系也可能是TOP 2A在17 q上紧密定位的结果。这两个基因HER-2和TOP 2A是否在不同的扩增子上单独起作用或一起起作用，从而使得有可能从HER-2状态预测TOP 2A状态，这一直是一个争论的问题。在这项研究中，TOP 2A，HER-2和17号染色体异倍体的荧光原位杂交（FISH）在50例连续乳腺癌患者进行了调查。HER-2扩增11例（22%），TOP 2A变化6例（12%）; HER-2扩增的情况下，观察到两个扩增和两个缺失，HER-2非扩增的情况下，两个缺失。TOP 2A缺失的病例中有3例为17号多体性。HER-2基因拷贝数高于TOP 2A基因拷贝数。多体性9例（18%），单体性6例（12%）。染色体异常是11例患者（22%）唯一的异常。我们得出结论，TOP 2A状态不能从HER-2状态预测，仅在HER-2过表达的患者中评价TOP 2A状态可能导致TOP 2A缺失的病例缺失，并可能对治疗产生耐药性。其他因素调节拓扑异构酶II α活性也可能影响对治疗的反应。研究评估不同的参数，可以调节拓扑异构酶II α活性和针对酶的药物的反应是必要的。
HER-2 amplification is a biomarker for identifying patients who respond to trastuzumab and has been evaluated as a factor predicting the response to anthracyclines. The relationship between HER-2 and response to anthracycline therapy may also be the result of the close localization of TOP2A on 17q. It has been a matter of debate whether these two genes, HER-2 and TOP2A, behave separately on different amplicons or act together thus making it possible to predict the TOP2A status from the HER-2 status. In this study TOP2A, HER-2 and chromosome 17 aneusomy were investigated by fluorescent in situ hybridization (FISH) in 50 consecutive breast cancer patients. HER-2 amplification was detected in 11 patients (22%) and TOP2A changes were seen in 6 patients (12%); two amplifications and two deletions were observed in HER-2-amplified cases and two deletions in HER-2-nonamplified cases. Three of the TOP2A-deleted cases had polysomy 17. HER-2 copy number was higher than the TOP2A copy number in one patient with co-amplification. Polysomy was observed in 9 cases (18%) and monosomy in 6 cases (12%). Aneusomy was the sole anomaly in 11 patients (22%). We conclude that the TOP2A status cannot be predicted from the HER-2 status and evaluation of the TOP2A status only in patients with HER-2 overexpression may lead to missing cases with TOP2A deletion with possible resistance to therapy. Other factors modulating topo II alpha activity may also affect the response to therapy. Studies evaluating different parameters that can modulate topo II alpha activity and the response to the drugs targeting the enzyme are necessary.