RT Journal Article SR Electronic T1 Frequent Mutation of Apc Gene in Rat Colon Tumors and Mucin-Depleted Foci, Preneoplastic Lesions in Experimental Colon Carcinogenesis JF Cancer Research JO Cancer Res FD American Association for Cancer Research SP 445 OP 449 DO 10.1158/0008-5472.CAN-06-3861 VO 67 IS 2 A1 Femia, Angelo Pietro A1 Dolara, Piero A1 Giannini, Augusto A1 Salvadori, Maddalena A1 Biggeri, Annibale A1 Caderni, Giovanna YR 2007 UL http://cancerres.aacrjournals.org/content/67/2/445.abstract AB Mucin-depleted foci (MDF) are microscopic dysplastic lesions induced in the colon of rodents by specific colon carcinogens. Most MDF show Wnt pathway activation, whereas only a subset shows mutations in the Ctnnb1 gene, coding for β-catenin. Because Apc is a member of the Wnt pathway and the most frequent mutated gene in human colon cancer, we tested whether MDF harbor Apc mutations. F344 rats were treated twice with 150 mg/kg of 1,2-dimethylhydrazine. After 15 or 28 weeks, MDF, aberrant crypt foci (ACF), and tumors were collected. We screened a segment of the Apc gene comprising the region homologous to the mutation cluster region (MCR) of human APC, which frequently shows mutations in experimental colon tumors. Mutations were identified by PCR amplification and sequencing in 6:24 MDF (25%), 7:23 tumors (30%), 0:24 ACF (0%). Most of the mutations (92%) in MDF and tumors were localized in a region upstream from the MCR. All mutations were single-base substitutions and mainly formed by G:C → A:T and C:G → T:A transitions. The pattern of nucleotide changes was similar in MDF and tumors, and, interestingly, the same mutation in codon 1047 was found in two MDF and in three tumors. Four out of the six mutations found in MDF were nonsense mutations, and two were missense. All mutations in tumors determined a protein truncation. These results show that Apc mutations are present in MDF with a frequency similar to that of tumors, strengthening the evidence that they are precancerous lesions in colon carcinogenesis. [Cancer Res 2007;67(2):445–9] ©2007 American Association for Cancer Research.