title: Novel germline CDH1 mutations in hereditary diffuse gastric cancer families.
abstract: Hereditary diffuse gastric cancer (HDGC) is a recently defined cancer syndrome caused by inactivating, heterozygous germline mutations in the gene for the cell-to-cell adhesion protein E-cadherin (CDH1). Here, we describe the search for CDH1 mutations in 10 newly identified gastric cancer families. Seven of 10 families met the clinical criteria for HDGC. Germline mutations were identified in four of these seven families and one family that was borderline for the clinical criteria. Of the mutations identified in the five new families, four were previously unreported and consisted of two frameshift and two donor splice site mutations. One splice site mutation occurred at the 100% conserved +1 position. The second splice site mutation occurred at the +5 position and was shown to lead to abnormal splicing. Additional CDH1 variants detected include the heterozygous -160 C-->A promoter polymorphism, which has previously been reported to be associated with decreased CDH1 transcription. We, however, found this polymorphism to be common in a control population, suggesting that a major role for this polymorphism in gastric cancer susceptibility is unlikely.
authors.affiliation: Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Bostjan
authors.initials: B
authors.lastname: Humar
authors.forename: Tumi
authors.initials: T
authors.lastname: Toro
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Müller
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Dobbie
authors.forename: Han
authors.initials: H
authors.lastname: Kwang-Yang
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Heather
authors.initials: H
authors.lastname: Hampel
authors.forename: Dale
authors.initials: D
authors.lastname: Gilbert
authors.forename: Ingrid
authors.initials: I
authors.lastname: Winship
authors.forename: Susan
authors.initials: S
authors.lastname: Parry
authors.forename: Robyn
authors.initials: R
authors.lastname: Ward
authors.forename: Mike
authors.initials: M
authors.lastname: Findlay
authors.forename: Alice
authors.initials: A
authors.lastname: Christian
authors.forename: Monica
authors.initials: M
authors.lastname: Tucker
authors.forename: Kathy
authors.initials: K
authors.lastname: Tucker
authors.forename: Tony
authors.initials: T
authors.lastname: Merriman
authors.forename: Parry
authors.initials: P
authors.lastname: Guilford
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D015820:Cadherins