COMPARATIVE-ANALYSIS OF MUTATIONS IN THE P53 AND K-RAS GENES IN PANCREATIC-CANCER

COMPARATIVE-ANALYSIS OF MUTATIONS IN THE P53 AND K-RAS GENES IN PANCREATIC-CANCER
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DOI:
10.1002/ijc.2910580207
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发表时间:
1994-07-15
影响因子:
6.4
通讯作者:
PERUCHO, M
PERUCHO, M
中科院分区:
医学1区
文献类型:
--
作者:
BERROZPE, G;SCHAEFFER, J;PERUCHO, M

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K-ros的密码子12突变发生在高比例的胰腺癌病例中。虽然有证据表明,p53突变也发生在这种肿瘤,很少有研究报告,迄今为止,没有比较K-ras和p53突变在相同的组织。采用单链构象多态性(single strand conformation polymorphism,SSCP)和PCR产物测序法检测p53基因突变;采用限制性片段长度多态性(artificial restriction fragment length polymorphism,RFLP)方法检测K-ros基因突变。30例原发性胰腺癌组织中有8例和4例转移性胰腺癌组织中有3例显示p53突变。17个胰腺癌细胞系中有15个存在p53突变。在2例病例中,在原始肿瘤和肿瘤衍生细胞系中鉴定出相同的p53突变。大多数p53突变存在于基因的外显子5-9。在23/32胰腺癌组织和14/17细胞系中鉴定出K-ras基因第12密码子突变。两种基因的突变类型之间无相关性。总之,K-ros和p53基因突变在胰腺癌中很常见。p53突变可能发生在转移性病变比原发性肿瘤更频繁,虽然进一步的工作是必要的调查这一点。(C)1994 Wiley-Liss,Inc.
Mutations in codon 12 of K-ros 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-ros 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-ros 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. (C) 1994 Wiley-Liss, Inc.