title: Characterization of the P373L E-cadherin germline missense mutation and implication for clinical management.
abstract: OBJECTIVE
  Hereditary diffuse gastric cancer (HDGC) is a cancer susceptibility syndrome caused by E-cadherin germline mutations. One-third of these mutations are of the missense type, representing a burden in genetic counselling. A new germline missense mutation (P373L) was recently identified in a HDGC Italian family. The present work aimed at addressing the disease-causative nature of the P373L mutant.
  
  
  METHODS
  Assessment of the P373L mutation effect was based on cell aggregation and invasion assays. LOH analysis at the E-cadherin locus, search for somatic E-cadherin mutations and for promoter hypermethylation were performed to identify the mechanism of inactivation of the E-cadherin wild-type allele in the tumour.
  
  
  RESULTS
  In vitro the P373L germline mutation impaired the E-cadherin functions. E-cadherin promoter hypermethylation was observed in the tumour of the P373L mutation carrier.
  
  
  CONCLUSIONS
  We conclude that the combination of clinical, in vitro and molecular genetic data is helpful for establishing an accurate analysis of HDGC-associated CDH1 germline missense mutations and subsequently for appropriate clinical management of asymptomatic mutation carriers.
authors: Department of Human Pathology and Oncology, Division of Surgical Oncology, University of Siena, Siena, Italy.
authors: G
authors: G
authors: Corso
authors: F
authors: F
authors: Roviello
authors: J
authors: J
authors: Paredes
authors: C
authors: C
authors: Pedrazzani
authors: M
authors: M
authors: Novais
authors: J
authors: J
authors: Correia
authors: D
authors: D
authors: Marrelli
authors: L
authors: L
authors: Cirnes
authors: R
authors: R
authors: Seruca
authors: C
authors: C
authors: Oliveira
authors: G
authors: G
authors: Suriano
mesh_terms: D019943:Amino Acid Substitution; D015820:Cadherins / Q000235:genetics*; D002353:Carrier State / Q000503:physiopathology; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D018095:Germ-Line Mutation; D006801:Humans; D020125:Mutation, Missense; D009361:Neoplasm Invasiveness / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D015820:Cadherins