Mulcahy H E, Lyautey J, Lederrey C, qi Chen X, Anker P, Alstead E M, Ballinger A, Farthing M J, Stroun M
Digestive Diseases Research Centre, St. Bartholomew's, London, United Kingdom.
Clin Cancer Res. 1998 Feb;4(2):271-5.
K-ras mutations are frequently found in primary pancreatic adenocarcinomas. In this prospective study, we looked for K-ras mutations in the plasma of patients with pancreatic cancer. We isolated plasma DNA from 21 pancreatic cancer patients using a simple and rapid extraction technique and detected K-ras alterations with a PCR assay and subsequent product sequencing. Patients were followed up to determine their clinical outcome. We found K-ras mutations in the plasma of 17 patients (81%). In cases in which both plasma and pancreatic tissue were available, DNA mutations were similar in corresponding plasma and tissue samples. Plasma DNA alterations were found 5-14 months before clinical diagnosis in four patients. Mutant DNA was not found in the plasma of two patients with chronic pancreatitis or in five healthy controls. Our results indicate that K-ras mutations are often found in DNA isolated from the plasma of pancreatic cancer patients and that a noninvasive plasma-based assay may provide qualitative diagnostic information to clinicians in the future. Larger studies are required to further assess the relevance of our findings to clinical practice.
K-ras突变在原发性胰腺腺癌中经常被发现。在这项前瞻性研究中，我们在胰腺癌患者的血浆中寻找K-ras突变。我们使用一种简单快速的提取技术从21例胰腺癌患者中分离血浆DNA，并通过聚合酶链反应（PCR）检测及后续产物测序来检测K-ras改变。对患者进行随访以确定其临床结局。我们在17例患者（81%）的血浆中发现了K-ras突变。在血浆和胰腺组织均可用的病例中，相应血浆和组织样本中的DNA突变相似。在4例患者中，血浆DNA改变在临床诊断前5至14个月被发现。在2例慢性胰腺炎患者的血浆或5例健康对照者中未发现突变DNA。我们的结果表明，K-ras突变经常在从胰腺癌患者血浆中分离的DNA中被发现，并且基于血浆的非侵入性检测方法未来可能为临床医生提供定性诊断信息。需要更大规模的研究来进一步评估我们的发现与临床实践的相关性。
