title: Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations.
abstract: OBJECTIVE
  Familial adenomatous polyposis is characterized by the development of hundreds of adenomatous polyps located mainly in the colon and rectum. Patients with familial adenomatous polyposis who do not receive treatment will develop cancer before aged 40 years. This disease is caused by germline mutations in the adenomatous polyposis coli gene. Different studies have shown a correlation between the location of the mutation and the clinical phenotype, such as the grade of severity and/or the presence of extracolonic manifestations, such as desmoid tumors. This study was designed to identify germline mutation in the adenomatous polyposis coli gene in Chilean families with familial adenomatous polyposis.
  
  
  METHODS
  We examined the adenomatous polyposis coli gene in 24 Chilean families with familial adenomatous polyposis. The adenomatous polyposis coli gene was screened for mutations combining single strand conformation polymorphism technique, protein truncation test, and DNA sequencing.
  
  
  RESULTS
  We detected 17 different truncating mutations in 21 of 24 families (87.5 percent); 9 of these were novel. Fourteen mutations were detected in exon 15, being the most frequent c.3,927_3,931delAAAGA, found in 3 of 21 families (14 percent). Eight families (33 percent) showed at least one patient affected with desmoid tumors, presenting mutations between codons 849 and 1,533. Interestingly, two mutations, c.3,632dupA and c.3,783_3,784delTT, leading into a truncating protein at codons 1,216 and 1,274, were associated with almost 100 percent penetrance for desmoid tumors among relatives.
  
  
  CONCLUSIONS
  We achieved 87 percent mutation detection rate in adenomatous polyposis coli gene; more than 50 percent of them were novel. The high percentage of novel mutations found may be because of the genetic composition of the Chilean population, which is an admixture of Amerindian and Spaniards, and the scarce information in the literature about similar populations.
authors.affiliation: Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Marjorie K
authors.initials: MK
authors.lastname: De la Fuente
authors.forename: Karin P
authors.initials: KP
authors.lastname: Alvarez
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Letelier
authors.forename: Felipe
authors.initials: F
authors.lastname: Bellolio
authors.forename: Mariana L
authors.initials: ML
authors.lastname: Acuña
authors.forename: Francisca S
authors.initials: FS
authors.lastname: León
authors.forename: Eliana
authors.initials: E
authors.lastname: Pinto
authors.forename: Pilar
authors.initials: P
authors.lastname: Carvallo
authors.forename: Francisco
authors.initials: F
authors.lastname: López-Köstner
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D002648:Child; D002677:Chile / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000235:genetics*; D005190:Family; D017491:Genes, APC / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence
chemical_list: D004273:DNA, Neoplasm