Uemura Takanori, Hibi Kenji, Kaneko Tetsuya, Takeda Shin, Inoue Soichiro, Okochi Osamu, Nagasaka Tetsuro, Nakao Akimasa
Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
J Gastroenterol. 2004 Jan;39(1):56-60. doi: 10.1007/s00535-003-1245-1.
In pancreatic cancers, K-ras mutations have been found frequently (80%-100%), and they could be a good marker to detect tumor DNA in the plasma. Several studies have indicated that polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis of K-ras mutation was a useful method for the detection of hepatic and lymph node metastasis of pancreatic cancer. However, this method sometimes exhibited false-positive results, and the rate of K-ras mutation might thus be overestimated in these tissues. To diagnose pancreatic cancer correctly at an early stage, we attempted to detect tumor DNA in the plasma of pancreatic cancer patients using a more sensitive and specific method.
We examined 28 pancreatic cancer patients using a sensitive mutation-specific mismatch ligation assay for K-ras gene mutations in primary tumors and paired plasma samples.
K-ras gene mutations were detected in 26 of the 28 (93%) pancreatic cancers. We also found the same mutations in 9 of these 26 (35%) patients in their plasma DNA. This mutation was found even in the plasma of patients with TNM stage II cancer.
Genetic alterations present in the tumors of pancreatic cancer patients can be detected in their plasma, and this approach is potentially applicable for cancer screening and the monitoring of this deadly disease.
在胰腺癌中,K-ras 突变经常被发现(80%-100%),它们可能是检测血浆中肿瘤 DNA 的良好标志物。几项研究表明,K-ras 突变的聚合酶链反应/限制性片段长度多态性(PCR/RFLP)分析是检测胰腺癌肝转移和淋巴结转移的一种有用方法。然而,该方法有时会出现假阳性结果,因此在这些组织中 K-ras 突变率可能被高估。为了早期正确诊断胰腺癌,我们尝试使用一种更灵敏、特异的方法检测胰腺癌患者血浆中的肿瘤 DNA。
我们使用一种灵敏的针对原发性肿瘤和配对血浆样本中 K-ras 基因突变的特异性错配连接检测法,对 28 例胰腺癌患者进行了检测。
28 例胰腺癌中有 26 例(93%)检测到 K-ras 基因突变。在这 26 例患者中的 9 例(35%)血浆 DNA 中也发现了相同的突变。甚至在 TNM 分期为 II 期癌症的患者血浆中也发现了这种突变。
胰腺癌患者肿瘤中存在的基因改变可以在其血浆中被检测到,这种方法有可能应用于癌症筛查以及对这种致命疾病的监测。