KRAS mutation profile in colorectal carcinoma and novel mutation--internal tandem duplication in KRAS

Oncogenic KRAS mutations are associated with resistance to anti-EGFR therapy in colorectal carcinoma. Since anti-EGFR monoclonal antibodies are employed in clinical practice in advanced colorectal cancer, KRAS mutations have become an important predictor of therapy outcome. Mutational analysis of KRAS was performed on 163 adenocarcinoma samples. Exons 1-3 of KRAS were analyzed using SSCP and sequencing. Fifty seven (35%) carcinomas had missense point mutations in one of codons 12, 13, 59, 61, 117. In accordance with the published data, missense mutations in codons 12 (66%) and 13 (22%) were the most frequent. Mutations in codons 59 and 117 occurred with the same frequency as in codon 61. The only detected insertion occurred in exon 2. 15-bp insertion resulted in tandem duplication of codons 62-66. Presumably, 5 additional amino acids affected switch II conformation and sustained Ras activity due to decreased GTP hydrolysis. We report this unusual new type mutation.