A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes
A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes
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DOI：
10.1093/hmg/ddg083
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发表时间：
2003-04-01
影响因子：
3.5
通讯作者：
Plass, C
中科院分区：
文献类型：
--
作者：
Dai, ZY;Zhu, WG;Plass, C
癌基因扩增是导致基因过表达并促进肿瘤发生的重要机制。扩增区域的鉴定可能具有预后和治疗意义。我们使用原发性肺癌和肺癌细胞系进行限制性标志基因组扫描（RLGS）以鉴定新的扩增序列。在非小细胞肺癌和小细胞肺癌的原发肿瘤和肺癌细胞系中观察到指示基因扩增的增强的RLGS片段。我们在染色体11 q22上鉴定了一种新的扩增子，除了先前报道的包括癌基因MYCC、MYCL 1的扩增子和先前鉴定的染色体区域6 q21和3q 26 -27的扩增子之外。11 q22的扩增在其他类型的癌症中也有报道，并被精确到类似于1.19 Mbp的区域，其完整序列是可用的。基于具有小区域低水平扩增的患者样本，我们能够将该区域进一步缩小至0.92 Mbp。位于该区域的基因包括两种细胞凋亡抑制剂（cIAP 1和cIAP 2）。免疫组织化学和蛋白质印迹分析确定cIAP 1和cIAP 2作为该区域的潜在癌基因，因为两者在具有或不具有较高拷贝数的多种肺癌中过表达。
Amplification of oncogenes is an important mechanism that can cause gene overexpression and contributes to tumor development. The identification of amplified regions might have both prognostic and therapeutic significance. We used primary lung carcinomas and lung cancer cell lines for restriction landmark genomic scanning (RLGS) to identify novel amplified sequences. Enhanced RLGS fragments that indicate gene amplification were observed in primary tumors and lung cancer cell lines of both non-small cell lung cancer and small cell lung cancer. We identified one novel amplicon on chromosome 11q22, in addition to previously reported amplicons that include oncogenes MYCC, MYCL1 and previously identified amplification of chromosomal regions 6q21 and 3q26-27. Amplification of 11q22 has been reported in other types of cancer and was refined to an similar to1.19 Mbp region for which the complete sequence is available. Based on a patient sample with a small region of low-level amplification we were able to further narrow this region to 0.92 Mbp. Genes localized in this region include two inhibitors of apoptosis (cIAP1 and cIAP2). Immunohistochemistry and western blot analysis identified cIAP1 and cIAP2 as potential oncogenes in this region as both are overexpressed in multiple lung cancers with or without higher copy numbers.