Hereditary diffuse gastric cancer and E-cadherin: description of the first germline mutation in an Italian family.
OBJECTIVE
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%).


CONCLUSIONS
The first CDH1 germline mutation of an Italian family is herein reported. The present missense mutation has never been described so far.
Roviello
F
F
Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Viale Bracci 2, 53100 Siena, Italy.
Corso
G
G
Pedrazzani
C
C
Marrelli
D
D
De Falco
G
G
Berardi
A
A
Garosi
L
L
Suriano
G
G
Vindigni
C
C
De Stefano
A
A
Leoncini
L
L
Seruca
R
R
Pinto
E
E
D015820:Cadherins / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
D015820:Cadherins; D004273:DNA, Neoplasm