Hereditary diffuse gastric cancer and E-cadherin: Description of the first germline mutation in an Italian family

Roviello, F.; Corso, G.; Pedrazzani, C.; Marrelli, D.; De Falco, G.; Berardi, A.; Garosi, L.; Suriano, G.; Vindigni, C.; De Stefano, A.; Leoncini, L.; Seruca, R.; Pinto, E.

doi:10.1016/j.ejso.2006.10.028

« Previous Next »European Journal of Surgical Oncology
Volume 33, Issue 4 , Pages 448-451, May 2007

Hereditary diffuse gastric cancer and E-cadherin: Description of the first germline mutation in an Italian family

F. Roviello
- Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Viale Bracci 2, 53100 Siena, Italy
G. Corso
- Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Viale Bracci 2, 53100 Siena, Italy
C. Pedrazzani
- Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Viale Bracci 2, 53100 Siena, Italy
- Corresponding author. Tel.: +39 577 585156; fax: +39 577 585157.
D. Marrelli
- Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Viale Bracci 2, 53100 Siena, Italy
G. De Falco
- Department of Human Pathology and Oncology, Unit of Pathology, University of Siena, Italy
- College of Science and Technology Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA
A. Berardi
- Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Viale Bracci 2, 53100 Siena, Italy
L. Garosi
- Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Viale Bracci 2, 53100 Siena, Italy
G. Suriano
- Institute of Molecular Pathology and Immunology of the University of Porto, University of Porto, Portugal
C. Vindigni
- Department of Human Pathology and Oncology, Unit of Pathology, University of Siena, Italy
A. De Stefano
- Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Viale Bracci 2, 53100 Siena, Italy
L. Leoncini
- Department of Human Pathology and Oncology, Unit of Pathology, University of Siena, Italy
R. Seruca
- Institute of Molecular Pathology and Immunology of the University of Porto, University of Porto, Portugal
E. Pinto
- Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Viale Bracci 2, 53100 Siena, Italy

Accepted 16 October 2006.

Abstract

Aims

Germline mutation of the E-cadherin gene (CDH1) accounts for the Hereditary Diffuse Gastric Cancer (HDGC) syndrome. Fourteen pedigrees with Diffuse Gastric Cancer that fulfilled the International Gastric Cancer Linkage Consortium (IGCLC) criteria were selected and screened for CDH1 germline mutations.

Methods

The entire coding region of the CDH1 gene and all intron–exon boundaries were analyzed by direct sequencing in the 14 families fulfilling the IGCLC criteria. E-cadherin immunohistochemical expression was evaluated on tumour as well as normal formalin-fixed paraffin embedded tissues.

Results

A novel germline missense mutation was found. It was a single C→T substitution in exon 8, resulting in a transition of CCG→CTG (C1118T; Pro373Leu) demonstrated in the proband and her brother. At immunohistochemical analysis, the staining intensity was reduced and considered weakly positive (15%).