Multiple mutations in the Kras gene in colorectal cancer: review of the literature with two case reports

• Published in: International journal of colorectal disease 2011-10, Vol.26 (10), p.1241-1248
• Main Authors: Macedo, Mariana Petaccia, Andrade, Louise De Brot, Coudry, Renata, Crespo, Rodrigo, Gomes, Marina, Lisboa, Bianca Cristina Garcia, Aguiar, Samuel, Soares, Fernando Augusto, Carraro, Dirce Maria, Cunha, Isabela Werneck
• Format: Article
• Language: English
• Subjects: Aged; Amino acids; Base Sequence; Biological and medical sciences; Cancer; Codon; Codon - genetics; Colorectal cancer; Colorectal Neoplasms - genetics; DNA Mutational Analysis; Female; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Genes; Genetic aspects; Hepatology; Humans; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Molecular Sequence Data; Mutation - genetics; Mutation Rate; Nucleotides - genetics; Panitumumab; Proctology; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Review; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery; Tumors
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-011-1238-0

Purpose Kras mutations are negative predictors of anti-EGFR therapy, occurring in 40% of colorectal carcinomas (CRCs). Point substitutions in codon 12 or 13 are the most frequent mutations in Kras , but multiple mutations (MMs) in other codons can also develop. Few data exist on MMs with regard to their frequency and the codons and amino acids that are affected. We report two cases of Kras double mutations in codons 12 and 13 and review Kras MMs in primary CRC in PubMed databases. Case report A 53-year-old woman and a 70-year-old man presented with deep, invasive, moderately differentiated CRC at an advanced clinical stage. The former had regional lymph node involvement and vaginal wall neoplastic implantation, and the latter had liver metastasis. Primary tumors were examined for Kras mutations by pyrosequencing, which were confirmed by direct sequencing. Both tumors had a mutation in codons 12 and 13, wherein codon 12 was mutated to GAT, and codon 13 became GAC. Conclusions We identified 69 reported cases of Kras MMs and reported two other cases, representing 2.1% of all mutated tumors; the incidence of such mutations is 1.0% in CRC patients. In most cases (59%), MMs develop in a single codon, usually codon 12. Codons 12 and 13 are affected simultaneously in only 27% of cases. These findings add information about the impact of specific amino acid changes in the Kras gene.