title: A study of ras gene mutations in colonic adenomas from familial polyposis coli patients.
abstract: Using an in vitro amplification step (polymerase chain reaction) followed by oligonucleotide dot blot analysis, DNA samples from 29 familial polyposis coli patients (75 polyp-derived and 26 'normal' colon samples with no epithelial atypia) were screened for the presence of K-, N-, and H-ras mutations. Only 5 polyps contained ras mutations (7%)--all in K-ras codon 12. In each case 'normal' colon DNA was available and found to be negative in this assay. We also report the detection of K-ras codon 12 mutations in a stably non-tumorigenic immortal adenoma-derived cell line, PC/AA, and in a tumorigenic colorectal carcinoma cell line, PC/JW. Both epithelial cell lines were derived from different FPC patients. An activated K-ras gene was also found in cell line S/AN, isolated from a sporadic villous adenoma. These results provide further evidence that there are common molecular events involved in sporadic and hereditary colorectal carcinogenesis and that K-ras mutations can precede the development of malignancy. To our knowledge PC/AA is the first reported example of a human cell line bearing a mutant ras gene that is not tumorigenic and shows that the presence of an activated ras gene even in an immortal human cell line is insufficient for malignancy.
authors.affiliation: Cell and Molecular Biology Section, Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Farr
authors.forename: C J
authors.initials: CJ
authors.lastname: Marshall
authors.forename: D J
authors.initials: DJ
authors.lastname: Easty
authors.forename: N A
authors.initials: NA
authors.lastname: Wright
authors.forename: S C
authors.initials: SC
authors.lastname: Powell
authors.forename: C
authors.initials: C
authors.lastname: Paraskeva
mesh_terms: D000236:Adenoma / Q000235:genetics*; D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002461:Cell Line, Transformed; D003110:Colonic Neoplasms / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D017931:DNA Primers; D005091:Exons; D011905:Genes, ras; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D016376:Oligonucleotides, Antisense