title: Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients.
abstract: We searched for germ-line mutations of the APC gene in 79 unrelated patients with familial adenomatous polyposis using a ribonuclease protection analysis coupled with polymerase chain reaction amplifications of genomic DNA. Mutations were found in 53 patients (67%); 28 of the mutations were small deletions and 2 were 1- to 2-base-pair insertions; 19 were point mutations resulting in stop codons and only 4 were missense point mutations. Thus, 92% of the mutations were predicted to result in truncations of the APC protein. More than two-thirds (68%) of the mutations were clustered in the 5' half of the last exon, and nearly two-fifths of the total mutations occurred at one of five positions. This information has significant implications for understanding the role of APC mutation in inherited forms of colorectal neoplasia and for designing effective methods for genetic counseling and presymptomatic diagnosis.
authors.affiliation: Department of Biochemistry, Cancer Institute, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: H
authors.initials: H
authors.lastname: Ando
authors.forename: H
authors.initials: H
authors.lastname: Nagase
authors.forename: I
authors.initials: I
authors.lastname: Nishisho
authors.forename: A
authors.initials: A
authors.lastname: Horii
authors.forename: Y
authors.initials: Y
authors.lastname: Miki
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: J
authors.initials: J
authors.lastname: Utsunomiya
authors.forename: S
authors.initials: S
authors.lastname: Baba
authors.forename: G
authors.initials: G
authors.lastname: Petersen
mesh_terms: D000236:Adenoma / Q000235:genetics*; D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D001483:Base Sequence; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D003062:Codon; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D016368:Frameshift Mutation; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D014481:United States
chemical_list: D003062:Codon; D004273:DNA, Neoplasm