title: Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil.
abstract: BACKGROUND
  Hereditary diffuse gastric cancer (HDGC) is a hereditary autosomal inherited syndrome associated with CDH1 germline mutations. In Brazil, gastrointestinal tumors are among the most prevalent tumor types and constitute a serious public health problem, especially in the northern and northeastern regions. This study aimed to investigate germline mutations, methylation pattern and genomic rearrangements in the CDH1 gene and quantitative changes in the DNA of HDGC patients in northern and northeastern Brazil.
  
  
  METHODS
  Twenty-seven DNA samples from the members of four families affected by HDGC were analyzed using array comparative genomic hybridization (aCGH), DNA sequencing and methylation pattern.
  
  
  RESULTS
  No evidence of gain and loss events or any rearrangements were found in any of the samples tested using aCGH. No promoter region hypermethylation was observed either. Two of the four families presented different types of germline mutations. The 185G > T and 1018A > G germline mutations detected in this study have been described in Asian and European families, respectively. The ancestors of the two families carrying these mutations had originated from those continents.
  
  
  CONCLUSIONS
  This is the first study to evaluate CDH1 gene germline mutations in Brazilian families with HDGC. In our study, 50% of the families showed no CDH1 gene alterations, and it is possible that in regions with a high incidence of gastric cancer, such as northern and northeastern Brazil, environmental factors might have induced the different genetic alterations analyzed in this study.
authors.affiliation: Biological Science Institute, Federal University of Para, Belem, PA 66075110, Brazil.
authors.forename: Caroline Aquino
authors.initials: CA
authors.lastname: Moreira-Nunes
authors.affiliation: Biological Science Institute, Federal University of Para, Belem, PA 66075110, Brazil.
authors.forename: Mariceli Baia Leão
authors.initials: MBL
authors.lastname: Barros
authors.affiliation: Biotecnology Institute, Federal Rural University of Amazon, Belem, PA 66077830, Brazil.
authors.forename: Bárbara
authors.initials: B
authors.lastname: do Nascimento Borges
authors.affiliation: Biological Science Institute, Federal University of Para, Belem, PA 66075110, Brazil.|Nucleus of Research in Oncology, Federal University of Para, Belem, PA 66073000, Brazil.
authors.forename: Raquel Carvalho
authors.initials: RC
authors.lastname: Montenegro
authors.affiliation: Center of Hematology and Hemotherapy of Para - HEMOPA Foundation, Belem, PA 66033000, Brazil.
authors.forename: Leticia Martins
authors.initials: LM
authors.lastname: Lamarão
authors.affiliation: Biological Science Institute, Federal University of Para, Belem, PA 66075110, Brazil.
authors.forename: Helem Ferreira
authors.initials: HF
authors.lastname: Ribeiro
authors.affiliation: Biological Science Institute, Federal University of Para, Belem, PA 66075110, Brazil.
authors.forename: Amanda Braga
authors.initials: AB
authors.lastname: Bona
authors.affiliation: Nucleus of Research in Oncology, Federal University of Para, Belem, PA 66073000, Brazil.
authors.forename: Paulo Pimentel
authors.initials: PP
authors.lastname: Assumpção
authors.affiliation: Molecular Neuro-oncogenetics Laboratory, Research Unit-Unidad de Investigación, Hospital Universitario La Paz, 28046 Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Rey
authors.affiliation: Genetics and Molecular Biology Laboratory, Federal University of Piaui, Parnaiba, PI 64049-550, Brazil.
authors.forename: Giovanny Rebouças
authors.initials: GR
authors.lastname: Pinto
authors.affiliation: Biological Science Institute, Federal University of Para, Belem, PA 66075110, Brazil.|Nucleus of Research in Oncology, Federal University of Para, Belem, PA 66073000, Brazil.
authors.forename: Rommel Rodriguez
authors.initials: RR
authors.lastname: Burbano
keywords: Array comparative genomic hybridization; CDH1; HDGC; Hereditary diffuse gastric cancer; aCGH