Distribution of some activating KRAS and BRAF mutations in Slovene patients with colorectal cancer.
Numerous clinical studies have shown that anti-EGFR therapies are effective only in a subset of patients with colorectal cancer. Even though mutations in the KRAS gene have been confirmed as negative predictors of the response to EGFR-targeted therapies, not all KRAS wild-type (wt-KRAS) patients will respond to treatment. Recent studies have demonstrated that additionally wild-type BRAF (wt-BRAF) genotype is required for response to panitumumab or cetuximab, suggesting that BRAF genotype criteria should be used together with KRAS genotype for selecting the patients who are about to benefit from the anti-EGFR therapy. In this study, 239 samples obtained from 215 patients with metastatic colorectal cancer were tested for the presence of the seven most common mutations in the KRAS gene and the V600E mutation in the BRAF gene. Among the tested patients, 53.8% of patients had wt-KRAS genotype and 46.2% were KRAS mutants. Around five percent (5.1%) of the tested patients bore the V600E mutation in BRAF gene. All the patients showing to have the V600E mutation in BRAF were wt-KRAS. The concordance of KRAS and BRAF mutational status between primary and metastatic tumor tissue samples was 100%. We have shown that the proportions of mutated and non-mutated KRAS in Slovene patients, as well as the proportion of V600E mutations in BRAF is similar to genotyping results reported by other authors. The tested seven KRAS mutations on codons 12 and 13 were mutually exclusive with the V600E mutation in the BRAF gene. Summing up the results about the KRAS and the BRAF mutation carriers from our study, the portion of potentially non-responsive patients for the anti-EGFR treatment is 51.3%.
Ličar
Alenka
A
Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Zaloška 2, 1000, Ljubljana, Slovenia.
Cerkovnik
Petra
P
Novaković
Srdjan
S
D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018154:Slovakia; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins