Novel CDH1 germline mutations identified in Chinese gastric cancer patients.

Abstract

AIM:

To give a comprehensive report of E-cadherin gene (CDH1) variations in a population at a high risk for gastric cancer (GC).

METHODS:

The samples consisted of 178 men and 58 women with a mean age of 62.3 ± 9.4 years and an age range of 30-84 years. A total of 240 cancer-free controls were recruited (mean age of 61.8 ± 10.1 years, age range of 26-82 years). Samples were screened for CDH1 germline mutations by high-resolution melting analysis or directly sequencing. Luciferase reporter assay, RNA splicing assay and bioinformatic analysis were used to evaluate the effect of mutations.

RESULTS:

Four novel CDH1 sequence alterations were identified in GC patients including a G>T transition 49 bp before the start codon; a three-nucleotide deletion, c.44_46del TGC; one missense mutation, c.604G>A (V202I); and one variation in the intron, c.1320+7A>G. In addition, polymorphism frequencies were observed for CDH1-164delT, -161C>A, -73A>C, c.48+6C>T, c.48+62_48+63delinsCGTGCCCCAGCCC, c.894C>T (A298A), c.1224G>A (A408A), c.1888C>G (L630V), c.2076T>C (A692A), and c.2253C>T (N751N) which is similar to the data reported in http://www.ncbi.nlm.nih.gov/projects/SNP/. RNA splicing analysis suggested that the c.1320+7A>G and c.1224G>A variations did not affect exon splicing ability. Luciferase reporter assay demonstrated that the c.-49T variation might be helpful for E-cadherin transcription, though the increase in transcription activity is limited (only 33%). SIFT score and PolyPhen analysis both demonstrated that the L630V missense mutation probably damages protein function, while the V202I variant does not.

CONCLUSION:

This study reveals novel mutations in sporadic GC patients which had been poorly investigated for susceptibility genes.

• Authors: Qin-Hua Chen, Wei Deng, Xiao-Wei Li, Xiu-Fang Liu, Jing-Mei Wang, Li-Feng Wang, Nong Xiao, Qiong He, Ya-Ping Wang, Yi-Mei Fan
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 19 Issue 6 Pg. 909-16 (Feb 14 2013) ISSN: 2219-2840 [Electronic] United States
• PMID: 23431106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• CDH1 protein, human
• Cadherins

Topics

• Adenocarcinoma (ethnology, genetics, metabolism, pathology)
• Adult
• Aged
• Aged, 80 and over
• Antigens, CD
• Asian People (genetics)
• Cadherins (genetics, metabolism)
• Case-Control Studies
• Chi-Square Distribution
• China (epidemiology)
• DNA Mutational Analysis
• Female
• Gene Expression Regulation, Neoplastic
• Genes, Reporter
• Genetic Predisposition to Disease
• Germ-Line Mutation
• HeLa Cells
• Humans
• Male
• Middle Aged
• Phenotype
• Risk Factors
• Stomach Neoplasms (ethnology, genetics, metabolism, pathology)