Chen QH, Deng W, Li XW, Liu XF, Wang JM, Wang LF, Xiao N, He Q, Wang YP, Fan YM. Novel CDH1 germline mutations identified in Chinese gastric cancer patients. World J Gastroenterol 2013; 19(6): 909-916 [PMID: 23431106 DOI: 10.3748/wjg.v19.i6.909]
Corresponding Author of This Article
Dr. Yi-Mei Fan, Associate Professor, Department of Medical Genetics, Medical School, Nanjing University, Hankou Road 22, Nanjing 210093, Jiangsu Province, China. ymfan@nju.edu.cn
Research Domain of This Article
Genetics & Heredity
Article-Type of This Article
Brief Article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Qin-Hua Chen, Wei Deng, Xiao-Wei Li, Xiu-Fang Liu, Ya-Ping Wang, Yi-Mei Fan, Department of Medical Genetics, Medical School, Nanjing University, Nanjing 210093, Jiangsu Province, China
Author contributions: Chen QH and Deng W contributed equally to this work; Fan YM conceived and designed the study, and drafted the manuscript; Deng W also helped to draft the manuscript; Chen QH and Deng W carried out mutation screening, case-control and bioinformatics analysis; Chen QH and Liu XF performed promoter luciferase activity assay; Li XW carried out RNA splicing analysis; Wang JM, Wang LF, Xiao N and He Q contributed to the collection of samples and clinical data; Wang YP reviewed and modified the paper; and all of the authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 30972535; the Natural Science Foundation of Jiangsu, China, No. BK2012724; the Fundamental Research Funds for the Central Universities of China, 1112021402
Correspondence to: Dr. Yi-Mei Fan, Associate Professor, Department of Medical Genetics, Medical School, Nanjing University, Hankou Road 22, Nanjing 210093, Jiangsu Province, China. ymfan@nju.edu.cn
Telephone: +86-25-83593374 Fax: +86-25-83686559
Received: July 9, 2012 Revised: December 4, 2012 Accepted: December 27, 2012 Published online: February 14, 2013 Processing time: 213 Days and 22.5 Hours
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.
