title: Role of specific DNA mutations in the peripheral blood of colorectal cancer patients for the assessment of tumor stage and residual disease following tumor resection.
abstract: In the present study, the detection of tumor-specific KRAS proto-oncogene, GTPase (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations in the peripheral blood of colorectal cancer (CRC) patients at all stages and adenomas was used for the estimation of disease stage prior to surgery and for residual disease following surgery. A total of 65 CRC patients were enrolled. The primary tumor tested positive for the specific mutations (KRASmutations in codons 12, 13, 61, 117 or 146 andBRAFmutations in codon 600) in 35 patients. In all these patients, the specimen of normal bowel resected with the tumor was also tested for the presence of the same mutations in order to exclude the germ-line mutations. Only patients who tested positive for the specific mutation in the primary tumor were included in further analysis for the presence of tumor-specific mutation in the peripheral blood. No statistically significant differences were found between the detection rates of tumor mutations in the blood and different tumor stages (P=0.491). However, statistically significant differences in the proportions of patients with detected tumor-specific DNA mutations in the peripheral blood were found when comparing the groups of patients with R0 and R2 resections (P=0.038). Tumor-specific DNA mutations in the peripheral blood were more frequently detected in the patients with an incomplete surgical clearance of the tumor due to macroscopic residual disease (R2 resections). Therefore, the study concludes that the follow-up of somaticKRAS- andBRAF-mutated DNA in the peripheral blood of CRC patients may be useful in assessing the surgical clearance of the disease.
authors.affiliation: Clinical Department of Abdominal Surgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Norcic
authors.affiliation: Clinical Department of Abdominal Surgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
authors.forename: Franc
authors.initials: F
authors.lastname: Jelenc
authors.affiliation: Department of Molecular Diagnostics, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia.
authors.forename: Petra
authors.initials: P
authors.lastname: Cerkovnik
authors.affiliation: Department of Molecular Diagnostics, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia.
authors.forename: Vida
authors.initials: V
authors.lastname: Stegel
authors.affiliation: Department of Molecular Diagnostics, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Novakovic
keywords: BRAF; CK20; KRAS; colorectal cancer; peripheral blood; residual disease; staging