title: Germline CDH1 mutations in bilateral lobular carcinoma in situ.
abstract: BACKGROUND
  Invasive lobular breast cancer (ILC) and lobular carcinoma in situ (LCIS) are characterised by loss of E-cadherin expression. However germline CDH1 mutations are rare in cases of ILC with no family history of hereditary diffuse gastric cancer (HDGC) and have not been described in women with LCIS.
  
  
  METHODS
  We screened the CDH1 gene in 50 cases of bilateral LCIS/ILC using Sanger sequencing and MLPA.
  
  
  RESULTS
  Sanger sequencing revealed four pathogenic germline mutations, including a novel splicing mutation (c.48+1G>A). The remaining three (c.1465insC, c.1942G>T, c.2398delC) have been previously described. All four cases had bilateral LCIS +/- ILC and no family history of gastric cancer.
  
  
  CONCLUSIONS
  CDH1 germline mutations have not been previously described in women with LCIS. We have shown that germline CDH1 mutations are associated with early onset of bilateral LCIS with or without ILC in women without a family history of gastric cancer. CDH1 mutation screening should be considered in women with early onset of bilateral LCIS/ILC with no family history of HDGC.
authors.affiliation: 1] Research Oncology, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK [2] Medical and Molecular Genetics, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: C
authors.initials: C
authors.lastname: Petridis
authors.affiliation: Research Oncology, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: I
authors.initials: I
authors.lastname: Shinomiya
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: K
authors.initials: K
authors.lastname: Kohut
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: P
authors.initials: P
authors.lastname: Gorman
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: M
authors.initials: M
authors.lastname: Caneppele
authors.affiliation: Research Oncology, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: V
authors.initials: V
authors.lastname: Shah
authors.affiliation: Research Oncology, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Troy
authors.affiliation: Research Oncology, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: Pinder
authors.affiliation: Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, St James's University Hospital, Leeds LS9 7TF, UK.
authors.forename: A
authors.initials: A
authors.lastname: Hanby
authors.affiliation: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: I
authors.initials: I
authors.lastname: Tomlinson
authors.affiliation: Medical and Molecular Genetics, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Trembath
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: R
authors.initials: R
authors.lastname: Roylance
authors.affiliation: Medical and Molecular Genetics, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Simpson
authors.affiliation: Research Oncology, Kings College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: Sawyer
mesh_terms: D015703:Antigens, CD; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000235:genetics*; D002278:Carcinoma in Situ / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000473:pathology; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D017422:Sequence Analysis, DNA
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins