[Detection of KRAS gene mutation and its clinical significance in colorectal adenocarcinoma]

Abstract

Objective: To explore the clinical significance of KRAS mutation detection in colorectal adenocarcinoma.

Methods: Paraffin-embedded tissue specimens were obtained from 440 patients with colorectal adenocarcinoma. The genomic DNA was extracted. Mutations of exon 2 of KRAS gene were examined by PCR and direct sequencing.

Results: Somatic mutations of KRAS gene were identified in 146 cases, with the mutation rate of 33.2% (146/440). Among these 146 patients, KRAS mutation involved codon 12 in 118 patients, including 35G > A (Gly12Asp, 62 cases), 35G > T (Gly12Val, 35 cases), 34G > T (Gly12Cys, 9 cases), 34G > A (Gly12Ser, 6 cases), 35G > C (Gly12Ala, 5 cases), and 34G > C (Gly12Arg, 1 case); in 27 patients the mutation involved codon 13, including 38G > A (Gly13Asp, 25 cases), 38G > C (Gly13 Val, 1 case) and 37G > T (Gly13 Cys, 1 case); and in one patient, the mutation involved codon 14 with 40G > A (Val14Ile). The status of KRAS or codon 12 mutations in colorectal adenocarcinoma was related to patients' gender (P = 0.021 and P = 0.030, respectively), and this significant correlation to females was conserved in clinical stage III (P = 0.007 and P = 0.003, respectively), but not in stages I, II, and IV. The status of KRAS or codon 12 mutations was also related to tumor stage. Between stage II and stage IV, the mutation rate of KRAS and codon 12 showed significant difference (P = 0.028 and 0.034, respectively). Between stage III and stage IV, only the codon 12 mutation rate showed significant difference (P = 0.011). Codon 13 mutation was not related to tumor stage.

Conclusion: About one third of patients with colorectal adenocarcinoma have KRAS gene mutation, which might be related to patients' gender; and could be consistently detected by PCR and direct sequencing.