Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands

• Type: Article in International Scientific Journal
• Date: 2003

Authors

Suriano, G (Author) Other; Oliveira, C (Author) Other; Ferreira, P (Author) Other; Machado JC (Author) FMUP; Bordin, MC (Author) Other; De Wever, O (Author) Other; Bruyneel, EA (Author) Other; Moguilevsky, N (Author) Other; Grehan, N (Author) Other; Porter, TR (Author) Other; Richards, FM (Author) Other; Hruban, RH (Author) Other; Roviello, F (Author) Other; Huntsman, D (Author) Other; Mareel, M (Author) Other; Carneiro F (Author) FMUP; Caldas, C (Author) Other; Seruca, R (Author) FMUP

Journal

Title: Human Molecular Genetics

Vol. 12

Pages: 575-582

ISSN: 0964-6906

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 150 Citations

Scopus - 158 Citations

Other information

Authenticus ID: P-000-HHT

DOI: 10.1093/hmg/ddg048

Abstract (EN): E-cadherin is involved in the formation of cell-junctions and the maintenance of epithelial integrity. Direct evidence of E-cadherin mutations triggering tumorigenesis has come from the finding of inactivating germline mutations of the gene (CDH1) in hereditary diffuse gastric cancer (HDGC). We screened a series of 66 young gastric cancer probands for germline CDH1 mutations, and two novel missense alterations together with an intronic variant were identified. We then analysed the functional significance of the two exonic missense variants found here as well as a third germline missense variant that we previously identified in a HGDC family. cDNAs encoding either the wild-type protein or mutant forms of E-cadherin were stably transfected into CHO (Chinese hamster ovary) E-cadherin-negative cells. Transfected cell-lines were characterized in terms of aggregation, motility and invasion. We show that a proportion of apparently sporadic early-onset diffuse gastric carcinomas are associated with germline alterations of the E-cadherin gene. We also demonstrate that a proportion of missense variants are associated with significant functional consequences, suggesting that our cell model can be used as an adjunct in deciding on the potential pathogenic role of identified E-cadherin germline alterations.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8