AIM: To study the role of CDH1/E-cadherin (E-cad) gene alteration profiles including mutation, loss of heterozygosity (LOH), promoter polymorphism and hypermethylation in mechanisms of CDH1 inactivation in gastric carcinoma (GC). METHODS: Specimens were collected surgically from 70 patients with GC. Allelotyping PCR and detection of LOH, denaturing high pressure liquid chromatography and DNA sequencing, restriction fragment length polymorphism analysis, methylation specific PCR, and immunohistochemical staining were used. RESULTS: Promoter polymorphism was not a major mechanism of E-cad inactivation. Only one truncating mutation was found in a diffuse type tumor (3%). Both LOH and promoter hypermethylation were major mechanisms of E-cad inactivation, but interestingly, there was a negative association between the fraction of allelic loss (LOH) in tumors and hypermethylation of CDH1. Therefore LOH and hypermethylation were two different tumorigenic pathways involved in GC. CONCLUSION: Given the findings that somatic mutation was extremely low and the relationship between LOH and hypermethylation was inverse, any two combinations of these three factors cannot fulfill the classical two-hit hypothesis of CDH1 inactivation. Thus, other mechanisms operating at the transcriptional level or at the post-translational level might be required to induce E-cadherin inactivation.
AIM: To study the role of CDH1/E-cadherin (E-cad) gene alteration profiles including mutation, loss of heterozygosity (LOH), promoter polymorphism and hypermethylation in mechanisms of CDH1 inactivation in gastric carcinoma (GC). METHODS: Specimens were collected surgically from 70 patients with GC. Allelotyping PCR and detection of LOH, denaturing high pressure liquid chromatography and DNA sequencing, restriction fragment length polymorphism analysis, methylation specific PCR, and immunohistochemical staining were used. RESULTS: Promoter polymorphism was not a major mechanism of E-cad inactivation. Only one truncating mutation was found in a diffuse type tumor (3%). Both LOH and promoter hypermethylation were major mechanisms of E-cad inactivation, but interestingly, there was a negative association between the fraction of allelic loss (LOH) in tumors and hypermethylation of CDH1. Therefore LOH and hypermethylation were two different tumorigenic pathways involved in GC. CONCLUSION: Given the findings that somatic mutation was extremely low and the relationship between LOH and hypermethylation was inverse, any two combinations of these three factors cannot fulfill the classical two-hit hypothesis of CDH1 inactivation. Thus, other mechanisms operating at the transcriptional level or at the post-translational level might be required to induce E-cadherin inactivation.
Authors: G Berx; A M Cleton-Jansen; K Strumane; W J de Leeuw; F Nollet; F van Roy; C Cornelisse Journal: Oncogene Date: 1996-11-07 Impact factor: 9.867
Authors: M J Bussemakers; R J van Moorselaar; L A Giroldi; T Ichikawa; J T Isaacs; M Takeichi; F M Debruyne; J A Schalken Journal: Cancer Res Date: 1992-05-15 Impact factor: 12.701
Authors: S Matsui; H Shiozaki; M Inoue; S Tamura; Y Doki; T Kadowaki; T Iwazawa; K Shimaya; A Nagafuchi; S Tsukita Journal: Virchows Arch Date: 1994 Impact factor: 4.064
Authors: B Mayer; J P Johnson; F Leitl; K W Jauch; M M Heiss; F W Schildberg; W Birchmeier; I Funke Journal: Cancer Res Date: 1993-04-01 Impact factor: 12.701
Authors: H Oka; H Shiozaki; K Kobayashi; H Tahara; S Tamura; M Miyata; Y Doki; K Iihara; N Matsuyoshi; S Hirano Journal: Virchows Arch A Pathol Anat Histopathol Date: 1992
Authors: Silvio Ken Garattini; Debora Basile; Monica Cattaneo; Valentina Fanotto; Elena Ongaro; Marta Bonotto; Francesca V Negri; Rosa Berenato; Paola Ermacora; Giovanni Gerardo Cardellino; Mariella Giovannoni; Nicoletta Pella; Mario Scartozzi; Lorenzo Antonuzzo; Nicola Silvestris; Gianpiero Fasola; Giuseppe Aprile Journal: World J Gastrointest Oncol Date: 2017-05-15