Molecular detection of codon 12 K-RAS mutations in circulating DNA from serum of colorectal cancer patients

Point mutations of the K-RAS gene at codon 12 are found in about 40% of cas es with colorectal cancer. The diagnostic implications of the detection of these mutations and their clinical utility are still unclear. The aim of th is study was to test both the feasibility of the detection of the mutated K -RAS gene in serum and its potential role in colorectal cancer detection an d monitoring. Codon 12 K-RAS mutations were examined in DNA extracted from the serum of 3 5 patients with colorectal cancer and were compared with the K-RAS status i n the corresponding primary tumor. Molecular detection was performed by the mutant-enriched PCR (ME-PCR) assay, a sensitive method capable of distingu ishing a small quantity of mutated DNA in the presence of abundant wild-typ e DNA. The occurrence of mutations was compared with clinicopathological pa rameters as well as CEA and CA19.9 serum levels. We found codon 12 K-RAS mutations in the tissue of 13/35 (37%) patients. Se rum mutations were detected in 5/13 (38.5%) patients with mutated K-RAS in the tissue. 26/35 (74%) patients showed an identical K-RAS pattern in tissu e and serum. No codon 12 K-RAS alterations were found in serum samples of 2 2 patients with benign gastrointestinal diseases. Elevated serum CEA levels were detected in 16 patients, four of whom also presented serum RAS mutati ons. Our results confirm that K-RAS mutations can be found in circulating DNA ex tracted from serum samples of patients with colorectal cancer and show that there is a correspondence between serum and tissue K-RAS patterns.