Clinical and functional characterization of the CDH1 germline variant c.1679C>G in three unrelated families with hereditary diffuse gastric cancer

European Journal of Human Genetics : EJHG
Laura Pena-CousoMiguel Urioste

Abstract

Germline changes in the CDH1 tumor suppressor gene predispose to diffuse gastric cancer and lobular breast cancer. In carriers of deleterious germline CDH1 variants, prophylactic gastrectomy is recommended. In case of germline missense variants, it is mandatory to assess the functional impact on E-cadherin, the protein encoded by CDH1, and to predict their clinical significance. Herein, we have identified a recurrent germline missense variant, c.1679C>G, segregating with gastric cancer in three unrelated Spanish families. Through genetic, transcriptional, in silico and in vitro studies, we demonstrate the deleterious effect of the c.1679C>G variant and its association with hereditary diffuse gastric cancer, providing relevant data to relatives and allowing an accurate genetic counseling.

References

Dec 1, 2012·Human Molecular Genetics·Ingrid P VogelaarNicoline Hoogerbrugge
May 28, 2013·Journal of Medical Genetics·Patrick R BenusiglioOlivier Caron
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Datasets Mentioned

BETA
SCV000693437

Methods Mentioned

BETA
transfection
flow cytometry

Software Mentioned

MutationTaster
FATHMM
Align

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