title: Presence of c.3956delC mutation in familial adenomatous polyposis patients from Brazil.
abstract: OBJECTIVE
  To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis (FAP) in northern Brazil.
  
  
  METHODS
  A total of 15 individuals diagnosed with FAP from 5 different families from the north of Brazil were analyzed in this study. In addition to patients with histopathological diagnosis of FAP, family members who had not developed the disease were also tested in order to identify mutations and for possible genetic counseling. All analyzed patients or their guardians signed a consent form approved by the Research Ethics Committee of the João de Barros Barreto University Hospital (Belem, Brazil). DNA extracted from the peripheral blood of a member of each of the affected families was subjected to direct sequencing. The proband of each family was sequenced to identify germline mutations using the Ion Torrent platform. To validate the detected mutations, Sanger sequencing was also performed. The samples from all patients were also tested for the identification of mutations by real-time quantitative polymerase chain reaction using the amplification refractory mutation system.
  
  
  RESULTS
  Through interviews with relatives and a search of medical records, it was possible to construct genograms for three of the five families included in the study. All 15 patients from the five families with FAP exhibited mutations in the APC gene, and all mutations were detected in exon 15 of the APC gene. In addition to the patients with a histological diagnosis of FAP, family members without disease symptoms showed the mutation in the APC gene. In the present study, we detected two of the three most frequent germline mutations in the literature: the mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956delC mutation was found in all families from this study, and suggests that this mutation was introduced in the population of the State of Pará through ancestor immigration (i.e., a de novo mutation that arose in one member belonging to this state from Brazil).
  
  
  CONCLUSIONS
  Regardless of its origin, the c.3956delC mutation is a strong candidate biomarker of this hereditary cancer syndrome in families of northern Brazil.
authors: Caroline Aquino Moreira-Nunes, Diego di Felipe Ávila Alcântara, Rommel Rodriguez Burbano, Biological Science Institute, Federal University of Pará, Belem 66075110, Brazil.
authors: Caroline Aquino
authors: CA
authors: Moreira-Nunes
authors: Caroline Aquino Moreira-Nunes, Diego di Felipe Ávila Alcântara, Rommel Rodriguez Burbano, Biological Science Institute, Federal University of Pará, Belem 66075110, Brazil.
authors: Diego di Felipe Ávila
authors: Dd
authors: Alcântara
authors: Caroline Aquino Moreira-Nunes, Diego di Felipe Ávila Alcântara, Rommel Rodriguez Burbano, Biological Science Institute, Federal University of Pará, Belem 66075110, Brazil.
authors: Sérgio Figueiredo
authors: SF
authors: Lima-Júnior
authors: Caroline Aquino Moreira-Nunes, Diego di Felipe Ávila Alcântara, Rommel Rodriguez Burbano, Biological Science Institute, Federal University of Pará, Belem 66075110, Brazil.
authors: Sandro Roberto de Araújo
authors: SR
authors: Cavalléro
authors: Caroline Aquino Moreira-Nunes, Diego di Felipe Ávila Alcântara, Rommel Rodriguez Burbano, Biological Science Institute, Federal University of Pará, Belem 66075110, Brazil.
authors: Juan Antonio
authors: JA
authors: Rey
authors: Caroline Aquino Moreira-Nunes, Diego di Felipe Ávila Alcântara, Rommel Rodriguez Burbano, Biological Science Institute, Federal University of Pará, Belem 66075110, Brazil.
authors: Giovanny Rebouças
authors: GR
authors: Pinto
authors: Caroline Aquino Moreira-Nunes, Diego di Felipe Ávila Alcântara, Rommel Rodriguez Burbano, Biological Science Institute, Federal University of Pará, Belem 66075110, Brazil.
authors: Paulo Pimentel
authors: PP
authors: de Assumpção
authors: Caroline Aquino Moreira-Nunes, Diego di Felipe Ávila Alcântara, Rommel Rodriguez Burbano, Biological Science Institute, Federal University of Pará, Belem 66075110, Brazil.
authors: Rommel Rodriguez
authors: RR
authors: Burbano
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001938:Brazil; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D040941:Heredity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor
keywords: APC; Colorectal cancer; Familial adenomatous polyposis; Torrent sequencing