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.
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: A R Brooks-Wilson; P Kaurah; G Suriano; S Leach; J Senz; N Grehan; Y S N Butterfield; J Jeyes; J Schinas; J Bacani; M Kelsey; P Ferreira; B MacGillivray; P MacLeod; M Micek; J Ford; W Foulkes; K Australie; C Greenberg; M LaPointe; C Gilpin; S Nikkel; D Gilchrist; R Hughes; C E Jackson; K G Monaghan; M J Oliveira; R Seruca; S Gallinger; C Caldas; D Huntsman Journal: J Med Genet Date: 2004-07 Impact factor: 6.318
Authors: M Ringwald; R Schuh; D Vestweber; H Eistetter; F Lottspeich; J Engel; R Dölz; F Jähnig; J Epplen; S Mayer Journal: EMBO J Date: 1987-12-01 Impact factor: 11.598
Authors: Giulia Massari; Francesca Magnoni; Giorgio Favia; Nickolas Peradze; Paolo Veronesi; Carlo La Vecchia; Giovanni Corso Journal: Cancers (Basel) Date: 2021-05-12 Impact factor: 6.639