title: Somatic mutational mechanisms involved in intestinal tumor formation in Min mice.
abstract: We have demonstrated previously that intestinal tumor formation in B6 Min/+ mice is always accompanied by loss of the wild-type adenomatous polyoposis coli (Apc) allele and that intestinal tumor multiplicity in B6 Min/+ mice can be significantly increased by treatment with a single dose of N-ethyl-N-nitrosourea (ENU). Here, we show that some tumors from ENU-treated Min/+ mice can form without complete elimination of Apc+. At least 25% of these tumors acquired somatic Apc truncation mutations. Interestingly, some ENU-induced tumors demonstrated loss of the Apc+ allelic marker examined by the quantitative PCR assay used here. Using two methods of mutation detection, we identified no Apc mutations in at least 12% of the tumors from ENU-treated B6 Min/+ mice. Finally, no H- or K-ras-activating mutations were detected in intestinal tumors from either untreated or ENU-treated Min/+ mice. The majority of somatic human APC mutations in intestinal tumors lead to APC truncation. Our results demonstrate that somatic Apc truncation mutations also frequently occur in ENU-induced intestinal tumors in Min mice.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Shoemaker
authors.forename: C
authors.initials: C
authors.lastname: Luongo
authors.forename: A R
authors.initials: AR
authors.lastname: Moser
authors.forename: L J
authors.initials: LJ
authors.lastname: Marton
authors.forename: W F
authors.initials: WF
authors.lastname: Dove
mesh_terms: D000483:Alleles; D000818:Animals; D002273:Carcinogens; D005038:Ethylnitrosourea; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D011905:Genes, ras; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation
chemical_list: D002273:Carcinogens; D005038:Ethylnitrosourea