title: Chromosome alterations and E-cadherin gene mutations in human lobular breast cancer.
abstract: We have studied a set of 40 human lobular breast cancers for loss of heterozygosity (LOH) at various chromosome locations and for mutations in the coding region plus flanking intron sequences of the E-cadherin gene. We found a high frequency of LOH (100%, 31/31) at 16q21-q22.1. A significantly higher level of LOH was detected in ductal breast tumours at chromosome arms 1p, 3p, 9p, 11q, 13q and 18q compared to lobular breast tumours. Furthermore, we found a significant association between LOH at 16q containing the E-cadherin locus and lobular histological type. Six different somatic mutations were detected in the E-cadherin gene, of which three were insertions, two deletions and one splice site mutation. Mutations were found in combination with LOH of the wild type E-cadherin locus and loss of or reduced E-cadherin expression detected by immunohistochemistry. The mutations described here have not previously been reported. We compared LOH at different chromosome regions with E-cadherin gene mutations and found a significant association between LOH at 13q and E-cadherin gene mutations. A significant association was also detected between LOH at 13q and LOH at 7q and 11q. Moreover, we found a significant association between LOH at 3p and high S phase, LOH at 9p and low ER and PgR content, LOH at 17p and aneuploidy. We conclude that LOH at 16q is the most frequent chromosome alteration and E-cadherin is a typical tumour suppressor gene in lobular breast cancer.
authors.affiliation: Department of Pathology, National University Hospital, Reykjavik, Iceland.
authors.forename: C
authors.initials: C
authors.lastname: Huiping
authors.forename: J R
authors.initials: JR
authors.lastname: Sigurgeirsdottir
authors.forename: J G
authors.initials: JG
authors.lastname: Jonasson
authors.forename: G
authors.initials: G
authors.lastname: Eiriksdottir
authors.forename: J T
authors.initials: JT
authors.lastname: Johannsdottir
authors.forename: V
authors.initials: V
authors.lastname: Egilsson
authors.forename: S
authors.initials: S
authors.lastname: Ingvarsson
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA
chemical_list: D015820:Cadherins