The hepatocyte nuclear factor 3 alpha gene, HNF3alpha (FOXA1), on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas.
The hepatocyte nuclear factor 3 alpha gene, HNF3alpha (FOXA1), on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas.
复制标题
DOI：
--
复制
发表时间：
2002
期刊：
影响因子：
11.2
通讯作者：
Lin Lin-Lin;Charles T. Miller;Jorge I. Contreras;M. Prescott;S. Dagenais;R. Wu;J. Yee;M. Orringer;David E. Misek;S. Hanash;T. Glover;D. Beer
中科院分区：
文献类型：
--
作者：
Lin Lin-Lin;Charles T. Miller;Jorge I. Contreras;M. Prescott;S. Dagenais;R. Wu;J. Yee;M. Orringer;David E. Misek;S. Hanash;T. Glover;D. Beer
基因组扩增在许多（如果不是所有）类型的人类恶性肿瘤中观察到，并且是肿瘤发生中显性作用癌基因激活的机制之一。在本研究中，三个扩增的限制性内切酶片段被确定在食管腺癌（P16）使用限制性标志基因组扫描二维凝胶技术。将这些片段克隆、测序并定位于染色体带14 q13。使用序列标记的位点扩增作图方法，我们通过筛选75个正常-肿瘤配对的食管样本来定义核心扩增域。在食管肿瘤中14 q13扩增的频率为6.7%，在分析的37%（86个肿瘤中的32个）的肿瘤中，扩增子在1个肿瘤中跨越>6 Mb，但包含在正常肺中平均表达的区域中或=2.5倍。HNF 3 α基因扩增在5个过度表达的肺肿瘤中的2个中检测到。这是第一次报道HNF 3 α在食管癌和肺腺癌中的扩增和过表达。HNF 3 α在食管和肺肿瘤中的扩增可能提示该基因在肿瘤发生中的潜在致癌作用。
Genomic amplification is observed in many, if not all, types of human malignancy and is one of the mechanisms for the activation of dominant-acting oncogenes in tumorigenesis. In the present study, three amplified restriction fragments were identified in an esophageal adenocarcinoma (P16) using the restriction landmark genome scanning two-dimensional gel technique. These fragments were cloned, sequenced, and mapped to chromosome band 14q13. Using the sequence tagged site-amplification mapping approach, we defined the core-amplified domain by screening 75 normal-tumor paired esophageal samples. The frequency of 14q13 amplification is 6.7% in esophageal tumors, and the amplicon spans >6 Mb in 1 tumor but is contained in a region or =2.5-fold of mean expression in normal lung) in 37% (32 of 86) of the tumors analyzed. Gene amplification of HNF3alpha was detected in 2 of the 5 overexpressed lung tumors examined. This is the first report of HNF3alpha amplification, and overexpression in esophageal and lung adenocarcinomas. Amplification of HNF3alpha in esophageal and lung tumors may suggest a potential oncogenic role for this gene in tumorigenesis.