Germ-Line Mutations of the APC Gene in 53 Familial Adenomatous Polyposis Patients

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-05, Vol.89 (10), p.4452-4456
• Main Authors: Miyoshi, Yasuo, Ando, Hiroshi, Nagase, Hiroki, Nishisho, Isamu, Horii, Akira, Miki, Yoshio, Mori, Takesada, Utsunomiya, Joji, Baba, Shozo, Petersen, Gloria, Hamilton, Stanley R., Kinzler, Kenneth W., Vogelstein, Bert, Nakamura, Yusuke
• Format: Article
• Language: English
• Subjects: Adenoma - genetics; Adenomatous Polyposis Coli - genetics; Amino acids; APC gene; APC genes; APC protein; Base Sequence; Biological and medical sciences; Chromosome Deletion; Chromosomes, Human, Pair 5; Codon; Codons; Deoxyribonucleic acid; DNA; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; Exons; familial adenomatous polyposis; Frameshift Mutation; Gastroenterology. Liver. Pancreas. Abdomen; genes; Genes, Tumor Suppressor; Genetic Linkage; Genetic mutation; Genetics; Germline mutation; Humans; Japan; Malformations; man; Medical research; Medical sciences; Molecular Sequence Data; Mutation; Point mutation; Polymerase chain reaction; Polymerase Chain Reaction - methods; Restriction fragment length polymorphism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; truncation; United States
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.10.4452

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.