Frequency and spectrum of mutations at codons 12 and 13 of the c-K-ras gene in human tumors.
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 end 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.
California Institute of Biological Research, La Jolla 92037.
G
G
Capella
S
S
Cronauer-Mitra
M A
MA
Pienado
M
M
Perucho
D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003062:Codon; D004273:DNA, Neoplasm / Q000235:genetics; D004067:Digestive System Neoplasms / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000502:physiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D020690:GTPase-Activating Proteins; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000502:physiology; D012334:RNA, Neoplasm / Q000235:genetics; D015398:Signal Transduction; D020703:ras GTPase-Activating Proteins
D003062:Codon; D004273:DNA, Neoplasm; D020690:GTPase-Activating Proteins; D011506:Proteins; D012334:RNA, Neoplasm; D020703:ras GTPase-Activating Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)