title: Direct sequencing analysis of exon 1 of the c-K-ras gene shows a low frequency of mutations in human pancreatic adenocarcinomas.
abstract: We have applied direct dideoxy sequencing of DNA fragments amplified in vitro by the polymerase chain reaction to the detection of mutations in exon 1 of the c-K-ras gene in human pancreatic adenocarcinomas. Four fresh frozen primary tumors, one metastatic tumor, and twelve formalin-fixed paraffin embedded tumors were analysed. Only three cases showed a possible mutation in codon 12 in a small population of cells, in contrast to the high frequency reported for this alteration with the RNAase A protection assay and allele-specific oligoxynucleotide hybridization. No major difference in sensitivity was found between DNA sequence analysis, and the latter method. Our results suggest that if c-K-ras mutations are indeed present in pancreatic adenocarcinomas at the high frequency reported by others, they must be confined to a small fraction of the cell population to escape detection by direct sequencing. Such a phenomenon would have implications for c-K-ras mutations in the pathogenesis of pancreatic adenocarcinomas.
authors.affiliation: Division of Hematology/Oncology, University of California, Los Angeles 90024-1678.
authors.forename: N F
authors.initials: NF
authors.lastname: Gonzalez-Cadavid
authors.forename: D
authors.initials: D
authors.lastname: Zhou
authors.forename: H
authors.initials: H
authors.lastname: Battifora
authors.forename: M
authors.initials: M
authors.lastname: Bar-Eli
authors.forename: M J
authors.initials: MJ
authors.lastname: Cline
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D003062:Codon; D005091:Exons; D011905:Genes, ras; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics*
chemical_list: D003062:Codon