Detection of K-ras mutations in the plasma DNA of pancreatic cancer patients

Background. 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. Methods. 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. Results. 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. Conclusions. 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.