title: Screening E-cadherin germline mutations in Italian patients with familial diffuse gastric cancer: an analysis in the District of Urbino, Region Marche, Central Italy.
abstract: OBJECTIVE
  Hereditary diffuse gastric cancer is a recently defined cancer syndrome caused by inactivating, heterozygous germline mutations in the E-cadherin gene (CDH1). To date, 16 truncating germline CDH1 mutations have been described in hereditary diffuse gastric cancer families in different ethnic groups, but so far, no investigation has been addressed to Italian patients. In the District of Urbino, Region Marche, Central Italy, gastric cancer is the most common tumor in men and it is the second in women after breast cancer. In this area, we investigated CDH1 mutations in patients who fulfilled the hereditary diffuse gastric cancer criteria.
  
  
  METHODS
  Consecutive patients with diffuse gastric cancer were considered eligible for the study. After pedigree analysis, patients who met the International Gastric Cancer Linkage Consortium criteria were studied for CDH1 mutations. After blood samples collection and DNA extraction, standard polymerase chain reaction and sequencing techniques were used for CDH1 analysis.
  
  
  RESULTS
  In a study population of 98 patients with diffuse gastric cancer, 11 patients (11%) showed familial clustering and 3 of them met the International Gastric Cancer Linkage Consortium criteria for hereditary diffuse gastric cancer. None of the 3 patients showed inactivating germline mutation in CDH1.
  
  
  CONCLUSIONS
  According to recent studies, the frequency of CDH1 inactivating germline mutations in patients who fulfil the hereditary diffuse gastric cancer criteria may be lower than that reported in early investigations. The results of the present study in a population of Italian patients seem to confirm these data. It is likely that unidentified mutations in CDH1 or other involved genes contribute to diffuse gastric cancer susceptibility.
authors.affiliation: Medical Oncology Unit, Hospital of Urbino, Italy. frada@tin.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Ruzzo
authors.forename: Italo
authors.initials: I
authors.lastname: Bearzi
authors.forename: Enrica
authors.initials: E
authors.lastname: Testa
authors.forename: Vittorio
authors.initials: V
authors.lastname: Lai
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
mesh_terms: D000328:Adult; D015820:Cadherins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D015820:Cadherins