Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with gastric cancer.
Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide. DNA methylation is the most studied epigenetic alteration, occurring through a methyl radical addition to the cytosine base adjacent to guanine. Many tumor genes are inactivated by DNA methylation in gastric cancer. We evaluated the DNA methylation status of ANAPC1, CDKN2A and TP53 by methylation-specific PCR in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosa in individuals from Northern Brazil. All gastric cancer samples were advanced stage adenocarcinomas. Gastric samples were surgically obtained at the João de Barros Barreto University Hospital, State of Pará, and were stored at -80 degrees C before DNA extraction. Patients had never been submitted to chemotherapy or radiotherapy, nor did they have any other diagnosed cancer. None of the gastric cancer samples presented methylated DNA sequences for ANAPC1 and TP53. CDKN2A methylation was not detected in any normal gastric mucosa; however, the CDKN2A promoter was methylated in 30.4% of gastric cancer samples, with 35% methylation in diffuse-type and 26.9% in intestinal-type cancers. CDKN2A methylation was associated with the carcinogenesis process for ~30% diffuse-type and intestinal-type compared to non-neoplastic samples. Thus, ANAPC1 and TP53 methylation was probably not implicated in gastric carcinogenesis in our samples. CDKN2A can be implicated in the carcinogenesis process of only a subset of gastric neoplasias.
Lima
E M
EM
Colegiado de Biomedicina, Universidade Federal do Piauí, Parnaíba, PI, Brasil.
Leal
M F
MF
Burbano
R R
RR
Khayat
A S
AS
Assumpção
P P
PP
Bello
M J
MJ
Rey
J A
JA
Smith
M A C
MA
Casartelli
C
C
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D064173:Anaphase-Promoting Complex-Cyclosome; D064189:Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
C577335:ANAPC1 protein, human; D064189:Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome