Hollstein M C, Smits A M, Galiana C, Yamasaki H, Bos J L, Mandard A, Partensky C, Montesano R
International Agency for Research on Cancer, Lyon, France.
Cancer Res. 1988 Sep 15;48(18):5119-23.
Primary esophageal squamous cell carcinomas from 41 patients were analyzed for the presence of proto-oncogene alterations associated with this malignancy. The occurrence of activating ras gene mutations in 25 tumors was determined using oligomer hybridization of target sequences amplified by polymerase chain reaction. We found no evidence for mutations in codons 12 and 61 of the H-ras, K-ras, and N-ras genes, nor in codon 13 of the K-ras and N-ras loci in any of these tumors. The apparent absence of activated ras oncogene in esophageal cancers represents a possible exception to the presence of these mutations found consistently in numerous other types of human malignancies, and is in striking contrast to the 40% prevalence of ras mutations in human colorectal cancers. Southern blot hybridization experiments with DNAs from tumors demonstrated amplification of the epidermal growth factor receptor gene (c-erbB) in two of 25 carcinomas. No amplification of the structurally related c-erbB2 (neu) gene was detected. In three out of 12 carcinomas, the level of epidermal growth factor receptor RNA was significantly higher than in normal esophageal mucosal tissue. Our results suggest that enhanced transcription of the epidermal growth factor receptor gene is associated with the development of some esophageal cancers.
对41例原发性食管鳞状细胞癌患者的肿瘤样本进行分析，以检测与该恶性肿瘤相关的原癌基因改变情况。利用聚合酶链反应扩增目标序列后进行寡聚体杂交，测定25例肿瘤中激活型ras基因突变的发生率。我们发现，在这些肿瘤中，H-ras、K-ras和N-ras基因的第12和61密码子以及K-ras和N-ras基因座的第13密码子均未发生突变。食管癌中明显不存在激活的ras癌基因，这可能是众多其他类型人类恶性肿瘤中均一致存在这些突变的一个例外情况，并且与人类结直肠癌中40%的ras突变发生率形成了鲜明对比。对肿瘤DNA进行的Southern印迹杂交实验表明，25例癌中有2例存在表皮生长因子受体基因（c-erbB）扩增。未检测到结构相关的c-erbB2（neu）基因扩增。在12例癌中的3例中，表皮生长因子受体RNA水平显著高于正常食管黏膜组织。我们的结果表明，表皮生长因子受体基因转录增强与部分食管癌的发生有关。
