The germline CDH1 c.48 G>C substitution contributes to cancer predisposition through generation of a pro-invasive mutation Journal Article
| Authors: | Zhang, L.; Xiao, A.; Ruggeri, J.; Bacares, R.; Somar, J.; Iqbal, S.; Ricker, C.; Melo, S.; Figueiredo, J.; Simões-Correia, J.; Seruca, R.; Shah, M. A. |
| Article Title: | The germline CDH1 c.48 G>C substitution contributes to cancer predisposition through generation of a pro-invasive mutation |
| 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 G>. 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 G>. C (Q16H) variant contributes to HDGC through the generation of a pathogenic missense mutation with loss of anti-invasive function. |
| Keywords: | adult; controlled study; young adult; human cell; exon; missense mutation; case report; cancer incidence; allele; cancer susceptibility; cancer cell culture; uvomorulin; molecular cloning; genetic transfection; messenger rna; plasmid; stomach cancer; rna stability; codon; invasion; dna determination; glutamine; genomic dna; histidine; complementary dna; mutant; family; chemical modification; cdh1; human; female; article; hereditary gastric cancer; cdh1 gene; nucleotide substitution |
| Journal Title: | Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis |
| Volume: | 770 |
| ISSN: | 0027-5107 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2014-12-01 |
| Start Page: | 106 |
| End Page: | 111 |
| Language: | English |
| DOI: | 10.1016/j.mrfmmm.2014.10.001 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 2 January 2015 -- Source: Scopus |
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