Detection of K-ras and p53 gene mutations in pancreatic juice for the diagnosis of intraductal papillary mucinous tumors

Detection of K-ras and p53 gene mutations in pancreatic juice for the diagnosis of intraductal papillary mucinous tumors
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DOI:
10.1097/00006676-199904000-00011
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发表时间:
1999-04-01
期刊:
影响因子:
2.9
通讯作者:
Okita, K
Okita, K
中科院分区:
医学4区
文献类型:
--
作者:
Kaino, M;Kondoh, S;Okita, K

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本研究的目的是调查K-rns癌基因和p53 turner抑制基因在胰液中的突变,并评估我们的方法诊断导管内乳头状粘液性肿瘤(IPMT)。方法:收集12例IPMT患者手术切除标本(8例癌,4例腺瘤)和8例无明显胰腺疾病者的胰液,提取DNA,采用聚合酶链反应-单链构象多态性(PCR-SSCP)分析和直接测序法检测两种基因。此外,通过相同的方法对手术切除的标本进行了两种基因的分析,并对p53过表达进行了化学研究。所有12例患者(100%)的胰液中检测到K-ras点突变,12例患者中有5例(42%)检测到p53突变。它们不仅在癌中检出,而且在腺瘤中也检出,在胰液和手术标本中检出的突变无差异。在没有胰腺疾病的任何病例中均未发现突变。提示K-ras和p53基因的改变是IPMT发生发展过程中的共同事件,对胰液中K-ras和p53基因的检测可作为IPMT术前诊断的一个有用工具。
The aim of this study was to investigate mutations of the K-rns oncogene and the p53 turner suppressor gene in pancreatic juice and to evaluate our method for the diagnosis of intraductal papillary mucinous tumors (IPMT). Pancreatic juice was collected endoscopically from 12 patients with IPMT who underwent surgical resection (eight carcinomas and four adenomas) and eight cases without evident pancreatic diseases, DNA was extracted and both genes were examined by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. In addition, surgically resected specimens were analyzed for both genes by the same methods, and p53 overexpression was investigated immunohistochemically. K-ras point mutations were detected in pancreatic juice from all 12 patients (100%) and p53 mutations were detected in five of 12 (42%). They were detected not only in carcinoma but also in adenoma and there was no difference between the mutations detected in pancreatic juice and surgical specimens. No mutations were found in any cases without pancreatic diseases. These findings suggest that alterations of K-ras and p53 gene are common events in the development of IPMT and that genetic analysis of them in pancreatic juice can be a useful tool for the clinical diagnosis of IPMT before surgery.