Desmoglein 2 is expressed abnormally rather than mutated in familial and sporadic gastric cancer.
Alterations of the cell adhesion molecule E-cadherin have been demonstrated in sporadic and hereditary gastric carcinomas. A cell adhesion molecule with functional similarity to E-cadherin is desmoglein 2 (Dsg2), a major component of the desmosomes. In this study, we investigated whether alterations of Dsg2 are involved in gastric carcinogenesis and whether germline mutations contribute to a genetic predisposition in familial gastric cancer patients with no germline mutations in the E-cadherin gene. Seventy-five formalin-fixed, paraffin-embedded tissues from 37 familial and 38 sporadic gastric carcinomas were analysed for Dsg2 expression by immunohistochemistry. DNA from 31 familial gastric cancer patients was analysed for germline mutations and five sporadic tumours were analysed for somatic mutations by DHPLC. Of the 75 tumours, 25 (33%) demonstrated abnormal (reduced and/or non-membrane-associated) Dsg2 expression. There was a trend towards more frequent abnormal expression in diffuse type (42%) than in intestinal type tumours (18%) (p = 0.066). One germline missense variant leading to a non-conservative amino acid change (c. 2810 C > A, Thr 937 Asn) was found in a familial gastric cancer patient with a diffuse type tumour. No somatic mutations were identified. The observed abnormal expression of Dsg2 protein suggests that this molecule is involved in the carcinogenesis of a subset of gastric carcinomas, in particular of the diffuse type. Somatic mutations in the gene do not seem to be a very frequent inactivation event and the finding of no clear pathogenic germline mutation rules out Dsg2 as a major gastric cancer predisposition gene.
Biedermann
Karin
K
Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Germany.
Vogelsang
Holger
H
Becker
Ingrid
I
Plaschke
Susanne
S
Siewert
Jörg Rüdiger
JR
Höfler
Heinz
H
Keller
Gisela
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D051301:Desmoglein 2; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000235:genetics; D005192:Family Health; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000235:genetics
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; C495314:DSG2 protein, human; D051301:Desmoglein 2; D051182:Desmogleins; D051180:Desmoplakins; D009363:Neoplasm Proteins