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DNA methylation profile in diffuse type gastric cancer: evidence for hypermethylation of the BRCA1 promoter region in early-onset gastric carcinogenesis

Author
BERNAL,CAROLINA

VARGAS,MACARENA

OSSANDÓN,FRANCISCO

SANTIBÁÑEZ,EUDOCIA

URRUTIA,JULIO

LUENGO,VÍCTOR

ZAVALA,LUIS F

BACKHOUSE,CLAUDIA

PALMA,MARIANA

ARGANDOÑA,JORGE

AGUAYO,FRANCISCO

CORVALÁN,ALEJANDRO

Full text
https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0716-97602008000300007
Abstract
Diffuse type gastric carcinoma is the most aggressive type of gastric cáncer. 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 pl4, pl6, pl5, p73, MGMT and SEMA3B (20-49%). Hierarchical clustering analysis reveáis four groups with different clinical features. The first was characterized by hypermethylation of BRCA1 and younger age (<45 years oíd), and the second by hypermethylation of pl4 and pl6 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 cáncer. Hypermethylation of BRCA1 associated with young age suggests a role in early-onset gastric carcinoma.
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Discipline
Artes, Arquitectura y UrbanismoCiencias Agrarias, Forestales y VeterinariasCiencias Exactas y NaturalesCiencias SocialesDerechoEconomía y AdministraciónFilosofía y HumanidadesIngenieríaMedicinaMultidisciplinarias
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Universidad de ChileUniversidad Católica de ChileUniversidad de Santiago de ChileUniversidad de ConcepciónUniversidad Austral de ChileUniversidad Católica de ValparaísoUniversidad del Bio BioUniversidad de ValparaísoUniversidad Católica del Nortemore

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