Wagata T, Shibagaki I, Imamura M, Shimada Y, Toguchida J, Yandell D W, Ikenaga M, Tobe T, Ishizaki K
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Cancer Res. 1993 Feb 15;53(4):846-50.
We analyzed mutations of the p53 gene by single-strand conformation polymorphism analysis of polymerase chain reaction products and direct sequencing through all coding exons and exon-intron junctions in 32 cases with esophageal squamous cell carcinoma. Mutations were detected in 15 of 32 (47%) tumor samples, in which G:C to T:A transversions were rather frequent (33%). Previously, we reported deletion of chromosome 17p where the p53 gene is located in 45% of Japanese esophageal squamous cell carcinoma, and here the relationship between mutation of the p53 gene and loss of 17p was analyzed. Mutations were observed in 12 of 16 patients with loss of 17p, whereas only 2 of 11 without loss were positive for mutations, suggesting that mutations of the p53 gene were closely associated with a 17p deletion. Furthermore, we immunohistochemically analyzed the expression of p53 protein in esophageal squamous cell carcinoma tumor tissues using a monoclonal antibody. Five of 6 tumors with missense mutations of the p53 gene were positively stained, while in tumors with nonsense mutations or without mutations of the p53 gene staining was very weak or negative. These results suggest a good correlation between mutations and abnormal expression of the p53 gene.
我们通过聚合酶链反应产物的单链构象多态性分析以及对32例食管鳞状细胞癌所有编码外显子和外显子-内含子连接区进行直接测序，分析了p53基因的突变情况。在32个肿瘤样本中的15个（47%）检测到了突变，其中G:C到T:A的颠换较为常见（33%）。此前，我们报道在45%的日本食管鳞状细胞癌中存在p53基因所在的17号染色体短臂缺失，在此分析了p53基因突变与17p缺失之间的关系。在16例有17p缺失的患者中有12例观察到突变，而在11例无17p缺失的患者中只有2例突变呈阳性，这表明p53基因突变与17p缺失密切相关。此外，我们使用单克隆抗体对食管鳞状细胞癌肿瘤组织中p53蛋白的表达进行了免疫组织化学分析。6例p53基因错义突变的肿瘤中有5例呈阳性染色，而在p53基因无义突变或无突变的肿瘤中染色非常弱或为阴性。这些结果表明p53基因突变与异常表达之间具有良好的相关性。
