title: APC promoter 1B deletion in seven American families with familial adenomatous polyposis.
abstract: Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome caused by mutations in the adenomatous polyposis coli (APC) gene. Clinical genetic testing fails to identify disease causing mutations in up to 20% of clinically apparent FAP cases. Following the inclusion of multiplex ligation-dependent probe amplification (MLPA) probes specific for APC promoter 1B, seven probands were identified with a deletion of promoter 1B. Using haplotype analysis spanning the APC locus, the seven families appear to be identical by descent from a common founder. The clinical phenotype of 19 mutation carriers is classical FAP with colectomy at an average age of 24. The majority of cases had a large number of duodenal and gastric polyps. Measurements of allele-specific expression of APC mRNA using TaqMan assay confirmed that relative expression in the allele containing the promoter 1B deletion was reduced 42-98%, depending on tissue type. This study confirms the importance of APC promoter deletions as a cause of FAP and identifies a founder mutation in FAP patients from the United States.
authors.affiliation: Huntsman Cancer Institute.
authors.forename: A K
authors.initials: AK
authors.lastname: Snow
authors.affiliation: Huntsman Cancer Institute.
authors.forename: T M F
authors.initials: TM
authors.lastname: Tuohy
authors.affiliation: Huntsman Cancer Institute.
authors.forename: N R
authors.initials: NR
authors.lastname: Sargent
authors.affiliation: Huntsman Cancer Institute.
authors.forename: L J
authors.initials: LJ
authors.lastname: Smith
authors.affiliation: Huntsman Cancer Institute.|Division of Gastroenterology.
authors.forename: R W
authors.initials: RW
authors.lastname: Burt
authors.affiliation: Huntsman Cancer Institute.|Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Neklason
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000737:chemistry / Q000235:genetics*; D000328:Adult; D000569:Americas; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D012333:RNA, Messenger
keywords: APC; APC promoter 1B; allelic imbalance; colon cancer; familial adenomatous polyposis; founder mutation