Format

Send to

Choose Destination
World J Gastroenterol. 2013 Feb 14;19(6):909-16. doi: 10.3748/wjg.v19.i6.909.

Novel CDH1 germline mutations identified in Chinese gastric cancer patients.

Author information

1
Department of Medical Genetics, Medical School, Nanjing University, Nanjing 210093, Jiangsu Province, China.

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.

KEYWORDS:

CDH1; Gastric cancer; Germline mutation; Luciferase reporter assay; RNA splicing analysis

PMID:
23431106
PMCID:
PMC3574889
DOI:
10.3748/wjg.v19.i6.909
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Baishideng Publishing Group Inc. Icon for PubMed Central
Loading ...
Support Center