Frequency and Spectrum of Mutations at Codons 12 and 13 of the C-K-ras Gene in Human Tumors

Abstract

The frequency of point mutations at codons 12 and 13 of the c-K-ras gene has been determined in a panel of more than 400 human tumors. Mutant c-K-ras genes were detected in about 75% of adenocarcinomas of the pancreas (n = 84); 40% of adenomas (n = 72) and carcinomas (n = 244) of the colon and rectum; 30% of carcinomas of the bile duct (n = 19); 25% of carcinomas of the lung (n = 92), and in lower frequency in other carcinomas, including liver, stomach, and kidney. No mutations were found in carcinomas of the breast, prostate, esophagus, and gall bladder, among others. Comparative analysis of the spectrum of mutations show that while G to A transitions were the most frequent mutations in pancreatic and colo-rectal tumors, G to T transversions were more prevalent in lung carcinomas. The aspartic acid mutation at codon 13 (GGC -* GAC) was relatively frequent in colo-rectal tumors but rare in pancreatic and lung carcinomas. The differences in the mutation spectrum of the c-K-ras gene in cancers of the gastrointestinal and respiratory tracts are suggestive of differential exposure to genotoxic agents.

Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma

“…The 4 peptides corresponded to the most frequent K-RAS mutations found in pancreatic adenocarcinoma. 3 Fifteen minutes prior to peptide injections, 40 g recombinant human GM-CSF (Leucomax; Schering-Plough, Cork, Ireland) in 0.1 ml saline were administered by i.d. injection.…”

Multiplex PCR/LDR for detection of K-ras mutations in primary colon tumors

“…Point mutations in the Kras gene occur early in the development of colorectal neoplasms and are found in 35 ± 50% of colorectal adenomas and cancers. Most of these K-ras mutations are localized on codon 12 and to a lesser degree at codons 13 and 61 (Bos, 1988;Breivik, 1994;Capella, 1991;Finkelstein, 1993;Forrester, 1987;Losi et al, 1992;Vogelstein, 1988). These amino acid residues play a critical role in GTP binding, and point mutations at these codons produce oncogenic p21 ras proteins that resist GTP hydrolysis and have constitutively active signaling function (Barbacid, 1987).…”

The detection of K-ras mutations in colorectal cancer using the amplification-refractory mutation system

“…Many studies have examined the association of K-ras mutations with CRC (Bos et al, 1987;Forrester et al, 1987;Vogelstein et al, 1988;Bos, 1989;Burmer and Loeb, 1989;Vogelstein et al, 1989;Capella et al, 1991;Oudejans et al, 1991;Sidransky et al, 1992;Bell et al, 1993;Finkelstein et al, 1993a and b;McLellan et al, 1993;Urosevic et al, 1993;Breivik et al, 1994;Moerkerk et al, 1994;Morrin et al, 1994;Giaretti et al, 1995;Hasegawa et al, 1995;Hayashi et al, 1995;Ranaldi et al, 1995;Carpenter et al, 1996;Span et al, 1996;Villa et al, 1996). However, there are significant differences in reported frequencies of K-ras mutations in CRC (McLellan et al, 1993).…”

“…A significant proportion of CRCs have mutations in the K-ras oncogene (Bos et al, 1987;Forrester et al, 1987;Vogelstein et al, 1988;Burmer and Loeb, 1989;Delattre et al, 1989;Fearon and Vogelstein, 1990;Capella et al, 1991;Oudejans et al, 1991;Offerhaus et al, 1992;Bell et al, 1993;Finkelstein et al, 1993a and b;McLellan et al, 1993;Peltomaki et al, 1993;Urosevic et al, 1993;Breivik et al, 1994;Moerkerk et al, 1994;Morrin et al, 1994;Tanaka et al, 1994;Giaretti et al, 1995;Span et al, 1996). We report a study using 301 DNA samples extracted from a colorectal tumour bank.…”

“…Although there are many examples of nucleic acid changes having potential as tumour markers (Bos et al, 1987;Forrester et al, 1987;Vogelstein et al, 1988;Burmer and Loeb, 1989;Delattre et al, 1989;Kern et al, 1989;Vogelstein et al, 1989; Fearon and Vogelstein, 1990;Jones and Buckley, 1990;Capella et al, 1991;El-Deiry et al, 1991;Oudejans et al, 1991;Stork et al, 1991;Laurent-Puig et al, 1992;Offerhaus et al, 1992;Sharrard et al, 1992;Bell et al, 1993;Finkelstein et al, 1993a and b;McLellan et al, 1993;Urosevic et al, 1993;Breivik et al, 1994;Dix et al, 1994;Magewu and Jones, 1994;Moerkerk et al, 1994;Morrin et al, 1994;Tanaka et al, 1994;Giaretti et al, 1995;Laird et al, 1995;Span et al, 1996), their value as clinical tools in cancer diagnosis, staging or even screening needs to be demonstrated and two important criteria must be met. First, adequate supplies of nucleic acid must be extracted from the clinical material; second, robust and accurate methods of analysis are required.…”