MDM2 gene amplification in esophageal carcinoma
MDM2 gene amplification in esophageal carcinoma
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DOI：
10.3892/or.2016.4578
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发表时间：
2016-04-01
期刊：
影响因子：
4.2
通讯作者：
Odenthal, Margarete
中科院分区：
文献类型：
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作者：
Michalk, Maike;Meinrath, Jeannine;Odenthal, Margarete
食道癌(EC)是西方国家最常见的恶性肿瘤之一，以食管腺癌(EAC)为代表，发病率呈上升趋势。尽管在分期、手术程序和术后治疗方面有所改进，EC患者的总体存活率仍然很低。小鼠双分钟蛋白2(MDM2)通过诱导肿瘤抑制蛋白TP53的降解而发挥癌基因的作用。为了解食管癌和鳞癌组织中MDM2基因的扩增情况，我们建立了定量聚合酶链式反应(QPCR)方法，对127例食管癌组织中MDM2基因的扩增情况进行了筛查。对MDM2基因拷贝数增高的食管癌进一步进行荧光原位杂交(FISH)和MDM2免疫染色分析。其中23例(18%)经qPCR证实MDM2基因拷贝数升高，1/3(6.3%)经FISH分析和标记的MDM2蛋白免疫染色显示为簇状荧光。MDM2基因扩增与TP53突变的发生无关。由于MDM2过度表达具有很高的治疗相关性，但FISH的成本很高，我们建议通过qPCR初步筛选MDM2拷贝数变异，然后对已鉴定的EC进行详细的FISH分析。
Esophageal cancer (EC) is one of the most common malignancies diagnosed in the Western world with an increasing incidence noted for esophageal adenocarcinoma (EAC). Despite improvements in staging, surgical procedures and postoperative treatments, the overall survival of patients with EC remains low. Murine double minute-2 (MDM2) acts as an oncogene by inducing the degradation of the tumor-suppressor protein TP53. In order to evaluate the MDM2 gene amplification status in EAC and squamous cell carcinoma (SCC), we established a quantitative PCR (qPCR) assay, screening a total of 127 esophageal carcinoma cases for MDM2 amplification. Esophageal carcinoma cases with enhanced MDM2 gene copy numbers were further analyzed by fluorescence in situ hybridisation (FISH) and MDM2 immunostaining. Among a total of 23 specimens (18%), identified by qPCR to possess elevated MDM2 gene copy numbers, one third (6.3%) showed a cluster-like fluorescence pattern by FISH analyses and marked MDM2 protein immunostaining. MDM2 gene amplifications did not correlate with the occurrence of TP53 mutations. Due to the high therapeutic relevance of MDM2 overexpression, but the high cost of FISH, we suggest a primary screening of MDM2 copy number variations by qPCR, followed by detailed FISH analysis of the identified ECs.