Skip Main Navigation Links Jump to Footer

Scopus Preview

Human Molecular GeneticsVolume 12, Issue 5, 1 March 2003, Pages 575-582

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

  • Suriano, G.,
  • Oliveira, C.,
  • Ferreira, P.,
  • Machado, J.C.,
  • Bordin, M.C.,
  • De Wever, O.,
  • Bruyneel, E.A.,
  • Moguilevsky, N.,
  • Grehan, N.,
  • Porter, T.R.,
  • Richards, F.M.,
  • Hruban, R.H.,
  • Roviello, F.,
  • Huntsman, D.,
  • Mareel, M.,
  • Carneiro, F.,
  • Caldas, C.,
  • Seruca, R.
  • View Correspondence (jump link)
  • aInst. Patol. Imuno. Mole. Univ., 4200 Porto, Portugal
  • bCancer Genomics Program, Department of Oncology, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
  • cFaculdade de Medicina, Hospital de S. João, 4200 Porto, Portugal
  • dLab. of Experimental Cancerology, UZG, B-9000 Ghent, Belgium
  • eService of Applied Genetics, Inst. of Biol./Molecular Medicine, B-6041 Gosselies, Belgium
  • fSec. of Medical/Molecular Genetics, Div. of Reproductive/Child Health, University of Birmingham, Birmingham B15 2TT, United Kingdom
  • gDepartment of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States
  • hIst. Policattedra Sci. Chirurgiche, Universita Degli Studi di Siena, 53100 Siena, Italy
  • iDept. of Pathology/Lab. Medicine, Univ. of British Columbia Vancouver, Vancouver, BC, Canada

Abstract

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 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.

Indexed keywords

EMTREE drug terms:complementary DNAuvomorulin
EMTREE medical terms:adultarticlecancer patientcarcinogenesiscell aggregationcell invasioncell junctioncell linecell motilityCHO cellcontrolled studydisease modelexonfemalegene functiongene inactivationgene mutationgenetic analysisgenetic associationgenetic screeninggenetic transfectiongenetic variabilitygerm lineheredityhumanhuman cellintronmajor clinical studymalemedical decision makingmissense mutationmultigene familynucleotide sequencepriority journalprotein functionstomach cancerwild type
MeSH:AdultAnimalsCadherinsCarbohydrate DehydrogenasesCHO CellsCricetinaeFemaleHumansMaleMiddle AgedMutation, MissenseStomach Neoplasms
Species Index:CricetinaeCricetulus griseus

Molecular Sequence Numbers:

EMBL,

Z13009(referenced)

Chemicals and CAS Registry Numbers:

uvomorulin, 112956-45-3;

Cadherins; Carbohydrate Dehydrogenases, EC 1.1.-; cellobiose-quinone oxidoreductase, EC 1.1.99.18

Funding details

Funding sponsor Funding number Acronym
Fonds Wetenschappelijk Onderzoek
Cancer Research UK
See opportunities
Fundação para a Ciência e a Tecnologia
See opportunities		POCTI/CBO/40820/2001,POCTI/35374/CBO/2000

  • 1

    This study was funded by grants from: Fundac¸ão para a Ciência e a Tecnologia, Portugal (projects: POCTI/35374/CBO/2000 and POCTI/CBO/40820/2001); FORTIS Verzekerngen and the Fund for Scientific Research, Flanders (FWO), Brussels, Belgium; and by Cancer Research UK.

  • ISSN: 09646906
  • CODEN: HMGEE
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1093/hmg/ddg048
  • PubMed ID: 12588804
  • Document Type: Article

  Caldas, C.; Cancer Genomics Program, Department of Oncology, University of Cambridge, United Kingdom;
© Copyright 2008 Elsevier B.V., All rights reserved. © MEDLINE® is the source for the MeSH terms of this document.

Cited by 133 documents

Guindalini, R.S.C. , Cormedi, M.C.V. , Maistro, S.
Frequency of CDH1 germline variants and contribution of dietary habits in early age onset gastric cancer patients in Brazil
(2019) Gastric Cancer
Obermair, F. , Rammer, M. , Burghofer, J.
Cleft lip/palate and hereditary diffuse gastric cancer: report of a family harboring a CDH1 c.687 + 1G > A germline mutation and review of the literature
(2019) Familial Cancer
Figueiredo, J. , Melo, S. , Carneiro, P.
Clinical spectrum and pleiotropic nature of CDH1 germline mutations
(2019) Journal of Medical Genetics
View details of all 133 citations
Inform me when this document is cited in Scopus:
Set citation alert Set citation feed
{"topic":{"name":"Stomach Neoplasms; Cadherins; Cancer HDGC","id":22583,"uri":"Topic/22583","prominencePercentile":86.12761,"prominencePercentileString":"86.128","overallScholarlyOutput":0},"dig":"2c4a82111084b6617c182069b7610e553a66443797b5c3b4c6a78bb5f7db2929"}

SciVal Topic Prominence

Topic:
Prominence percentile: