Berrozpe G, Schaeffer J, Peinado M A, Real F X, Perucho M
Department d'Immunologia, Universitat Autònoma de Barcelona, Spain.
Int J Cancer. 1994 Jul 15;58(2):185-91. doi: 10.1002/ijc.2910580207.
Mutations in codon 12 of K-ras occur in a high proportion of pancreatic cancer cases. Although there is evidence that p53 mutations also occur in this tumor, few studies have been reported to date and no comparison has been made of K-ras and p53 mutations in the same tissues. Single-strand conformation polymorphism and sequencing of the PCR products were used to determine mutations in p53 gene; to detect mutations in K-ras genes, the artificial restriction fragment length polymorphism (RFLP) approach was used. Eight out of 30 tissues from primary pancreas cancer and 3 of 4 samples from metastases showed p53 mutations. Fifteen out of 17 pancreatic cancer cell lines had p53 mutations. In 2 cases, the same p53 mutation was identified in the original tumor and in a tumor-derived cell line. The majority of p53 mutations were present in exons 5-9 of the gene. Mutations at codon 12 of the K-ras gene were identified in 23/32 pancreas cancer tissues and in 14/17 cell lines. There was no relationship between the types of mutation observed in the 2 genes. In conclusion, mutations in K-ras and p53 genes are common in pancreatic cancer. p53 mutations may occur more frequently in metastatic lesions than in primary tumors, although further work is necessary to investigate this point.
在胰腺癌病例中，K-ras基因第12密码子的突变发生率很高。虽然有证据表明p53基因在这种肿瘤中也会发生突变，但迄今为止报道的研究很少，并且尚未对同一组织中的K-ras和p53突变进行比较。采用单链构象多态性和PCR产物测序来确定p53基因的突变；为检测K-ras基因的突变，采用了人工限制性片段长度多态性（RFLP）方法。30例原发性胰腺癌组织中有8例以及4例转移灶样本中有3例显示出p53突变。17株胰腺癌细胞系中有15株存在p53突变。在2例病例中，在原发肿瘤和肿瘤衍生的细胞系中鉴定出相同的p53突变。大多数p53突变存在于该基因的第5至9外显子中。在23/32例胰腺癌组织和14/17株细胞系中鉴定出K-ras基因第12密码子的突变。在这两个基因中观察到的突变类型之间没有关联。总之，K-ras和p53基因的突变在胰腺癌中很常见。p53突变在转移灶中可能比在原发性肿瘤中更频繁地发生，不过还需要进一步研究来证实这一点。
