title: Concurrent mutation in exons 1 and 2 of the K-ras oncogene in colorectal cancer.
abstract: The K-ras gene is frequently mutated in colorectal cancer and has been associated with tumor initiation and progression; approximately 90% of the activating mutations are found in codons 12 and 13 of exon 1 and just under 5% in codon 61 located in exon 2. These mutations determine single aminoacidic substitutions in the GTPase pocket leading to a block of the GTP hydrolytic activity of the K-ras p21 protein, and therefore to its constitutive activation. Point mutations in sites of the K-ras gene, other than codons 12, 13 and 61, and other types of genetic alterations, may occur in a minority of cases, such as in the less frequent cases of double mutations in the K-ras gene. However, all mutations in this gene, even those which occur in non-canonical sites or double mutations, are relevant oncogenic alterations in colorectal cancer and may underlie K-ras pathway hyperactivation. In the present study, we report the case of a patient with colorectal cancer presenting a concurrent point mutation in exons 1 and 2 of the K-ras gene, a GGT to TGT substitution (Glycine to Cysteine) at codon 12, and a GAC to AAC substitution (Aspartic Acid to Asparagine) at codon 57. In addition, we found in the same patient's sample a silent polymorphism at codon 11 (Ala11Ala) of exon 1.
authors.affiliation: Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy. raffaele.palmirotta@sanraffaele.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palmirotta
authors.forename: Annalisa
authors.initials: A
authors.lastname: Savonarola
authors.forename: Giorgia
authors.initials: G
authors.lastname: Ludovici
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: De Marchis
authors.forename: Renato
authors.initials: R
authors.lastname: Covello
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Ettorre
authors.forename: Cristiano
authors.initials: C
authors.lastname: Ialongo
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
mesh_terms: D001483:Base Sequence; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005091:Exons; D011905:Genes, ras; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D003062:Codon