title: DNA methylation profile in diffuse type gastric cancer: evidence for hypermethylation of the BRCA1 promoter region in early-onset gastric carcinogenesis.
abstract: Diffuse type gastric carcinoma is the most aggressive type of gastric cancer. This type of tumor is not preceded by precancerous changes and is associated with early-onset and hereditary syndromes. To test the hypothesis that DNA methylation profile would be useful for molecular classification of the diffuse type gastric carcinoma, DNA methylation patterns of the CpG Island of 17 genes were studied in 104 cases and 47 normal adjacent gastric mucosa by Methylation-specific PCR, Immunohistochemistry and Hierarchical clustering analysis. The most frequent methylated genes were FHIT, E-cadherin, BRCA1 and APC (>50%), followed by p14, p16, p15, p73, MGMT and SEMA3B (20-49%). Hierarchical clustering analysis reveals four groups with different clinical features. The first was characterized by hypermethylation of BRCA1 and younger age (<45 years old), and the second by hypermethylation of p14 and p16 genes, male predominance and Epstein-Barr virus infection. The third group was characterized by hypermethylation of FHIT and antrum located tumors and the fourth was not associated with any clinical variables. In normal adjacent mucosa only the p73 gene was significantly less methylated in comparison to tumor mucosa. DNA methylation identified subgroups of diffuse type gastric cancer. Hypermethylation of BRCA1 associated with young age suggests a role in early-onset gastric carcinoma.
authors.affiliation: Departmento Anatomía Patológica, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Bernal
authors.forename: Macarena
authors.initials: M
authors.lastname: Vargas
authors.forename: Francisco
authors.initials: F
authors.lastname: Ossandón
authors.forename: Eudocia
authors.initials: E
authors.lastname: Santibáñez
authors.forename: Julio
authors.initials: J
authors.lastname: Urrutia
authors.forename: Víctor
authors.initials: V
authors.lastname: Luengo
authors.forename: Luis F
authors.initials: LF
authors.lastname: Zavala
authors.forename: Claudia
authors.initials: C
authors.lastname: Backhouse
authors.forename: Mariana
authors.initials: M
authors.lastname: Palma
authors.forename: Jorge
authors.initials: J
authors.lastname: Argandoña
authors.forename: Francisco
authors.initials: F
authors.lastname: Aguayo
authors.forename: Alejandro
authors.initials: A
authors.lastname: Corvalán
mesh_terms: D016000:Cluster Analysis; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D042241:Early Diagnosis; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D019398:Genes, BRCA1; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm