Soman N R, Correa P, Ruiz B A, Wogan G N
Division of Toxicology, Whitaker College of Health Sciences and Technology, Cambridge, MA.
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4892-6. doi: 10.1073/pnas.88.11.4892.
The TPR-MET oncogenic rearrangement was originally observed in an in vitro transformed human osteosarcoma cell line. Recently, we detected the expression of this rearrangement at very low levels in several cell lines derived from human tumors of nonhematopoietic origin using a highly sensitive method based on polymerase chain reaction amplification of the transcript. We report here the results of analysis of TPR-MET expression in cell lines derived from human gastric tumors and 22 biopsy samples of human gastric mucosa showing cancer or precursor lesions. The rearranged RNA was expressed in all four cell lines as well as in biopsy samples from 12 of the 22 patients. Overexpression of TPR-MET RNA in superficial gastritis lesions with hyperplasia of glandular neck cells suggests the possible involvement of this oncogene at an early stage of gastric tumorigenesis. Analysis of gastric biopsy samples for RAS gene mutations showed base substitutions occurring in the codon 12 region of Ki- and Ha-RAS genes in four cases, including two precursor lesions.
TPR-MET致癌重排最初是在体外转化的人骨肉瘤细胞系中观察到的。最近,我们使用基于转录本聚合酶链反应扩增的高灵敏度方法,在几种源自非造血系统来源的人类肿瘤的细胞系中检测到这种重排的低水平表达。我们在此报告源自人胃肿瘤的细胞系以及显示癌症或癌前病变的22份人胃黏膜活检样本中TPR-MET表达的分析结果。重排的RNA在所有四个细胞系以及22例患者中12例的活检样本中均有表达。在伴有腺颈部细胞增生的浅表性胃炎病变中TPR-MET RNA的过表达表明该致癌基因可能在胃肿瘤发生的早期阶段就参与其中。对胃活检样本进行RAS基因突变分析显示,4例患者(包括2例癌前病变)的Ki-和Ha-RAS基因密码子12区域发生了碱基替换。