Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8455791 | Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis | 2014 | 6 Pages |
Abstract
Mutation screening of CDH1 is a standard of care for patients who meet criteria for Hereditary Diffuse Gastric Cancer (HDGC). In this setting, the classification of the sequence variants found in CDH1 is a critical step for risk management of patients with HDGC. In this report, we describe a germline CDH1 c.48 GÂ >Â C variant found in a 21 year old woman and her living great uncle, who were both diagnosed with gastric cancer and belong to a family with high incidence of this type of cancer. This variant occurs at the last nucleotide of exon 1 and presumably results in a Gln-to-His change at codon 16 (Q16H). We used cloning strategies to evaluate the effects on mRNA stability and found that 5/27 and 0/17 clones have the “C” mutant allele in patient and her great uncle, respectively. In vitro functional studies revealed that the germline missense mutant (Q16H) had a pro-invasive cell behavior. Both results (functional and clinical) support the conclusion that the CDH1 c.48 GÂ >Â C (Q16H) variant contributes to HDGC through the generation of a pathogenic missense mutation with loss of anti-invasive function.
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Authors
Liying Zhang, Alexander Xiao, Jeanine Ruggeri, Ruben Bacares, Joshua Somar, Soraia Melo, Joana Figueiredo, Joana Simões-Correia, Raquel Seruca, Manish A. Shah,