title: Truncating somatic mutation in exon 15 of the APC gene is a rare event in human breast carcinomas. Mutations in brief no. 179. Online.
abstract: Inactivation of the adenomatous polyposis coli (APC) gene is an early event in sporadic colorectal cancer. Somatic mutations have also been detected in cancers of the stomach, pancreas, thyroid, ovary and breast. Over 95% of the mutations reported in the APC gene are frameshift and nonsense mutations. The large exon 15 accounts for 77% of the coding sequence. The APC gene product interacts with cytoplasmic beta-catenin, mediates its degradation and thereby downregulates transcription exerted by the beta-catenin-Tcf complex. In the absence of a functional APC protein, beta-catenin is stabilized and accumulates in the cytoplasm. This results in uncontrolled transcriptional activation of Tcf responsive genes which may contribute to cancer progression. In order to investigate whether this pathway is disrupted by APC mutations in breast carcinoma cells, we screened 227 breast tumors for truncating mutations in exon 15 using the protein truncation test (PTT). Only one mutation, 4678delA, which was shown to be somatic, was detected by this approach. The mutation resided just outside the mutation cluster region (MCR) and resulted in a premature stop in codon 1564. Our findings do not indicate that the suppressive function of APC is commonly abrogated by truncating mutations in human breast carcinomas.
authors.affiliation: Dep. of Genetics, Inst. for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo.
authors.forename: T
authors.initials: T
authors.lastname: Sørlie
authors.forename: I
authors.initials: I
authors.lastname: Bukholm
authors.forename: A L
authors.initials: AL
authors.lastname: Børresen-Dale
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D005091:Exons / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D017491:Genes, APC / Q000235:genetics*; D006801:Humans
chemical_list: D018389:Codon, Nonsense