Somatic mutation screening: Identification of individuals harboring K-ras mutations with the use of plasma DNA

Background: Many cancers are attributed to somatic mutation of DNA, We inve stigated whether it is feasible to detect cancer-associated somatic mutatio ns in patients with neoplasms by using plasma DNA. Methods: Plasma samples were prospectively collected from 240 patients undergoing colonoscopy. Colo rectal biopsies were performed as clinically indicated in 135 patients, and risk factor information was available from 232 patients. DNA was extracted from plasma and colorectal tissue and was amplified by use of a polymerase chain reaction method that enriches for mutations in codon 12 of the K-ras oncogene, Molecular, histologic, and clinical data were compared by use of two-sided Fisher's exact test. Results: Mutations in the K-ras gene detect ed in the plasma of 64 (28%) of 232 patients were statistically significant ly associated with colorectal cancer risk factors (P = .0002). Of those pat ients having tissue available for comparison (n = 135), mutations in the K- ras gene were found in the tissues of 35 patients, and 29 (83%) of these 35 showed mutations in plasma samples. In contrast, the plasma assay was nega tive in 93 of the 100 patients whose tissue K-ras was wild-type, Among pati ents without biopsies (n = 105), 28 had mutated K-ras in their plasma DNA, despite the absence of remarkable colonoscopy findings; 24 of these 28 pati ents had risk factors for colorectal cancer, Overall, 25 (39%) of 64 patien ts showing mutations in plasma DNA had colorectal neoplasms with K-ras muta tions compared with five (3%) of 176 patients without K-ras mutations in pl asma DNA, Conclusion: Plasma DNA assays for the detection of mutations in K -ras codon 12 may provide a feasible method to screen populations for somat ic mutations frequently found in neoplasms. The clinical utility of using t his test in screening populations requires further study.