Abstract
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.
Highlights
Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide [1]
Three genes were chosen for evaluation considering their function and/or their potential role in gastric carcinogenesis: ANAPC1, CDKN2A and TP53
We evaluated the methylation status of ANAPC1, CDKN2A and TP53 promoters in gastric adenocarcinoma samples and their possible associations with clinical and pathological characteristics, such as gender, age, histopathology, tumor extension, and presence of lymph node or distant metastasis
Summary
Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide [1]. In Northern Brazil, gastric cancer is the second most frequent neoplasia in males (11/100,000) and the third most common in females (6/100,000) [2]. DNA methylation is the most studied epigenetic alteration, occurring by the addition of a methyl radical to the cytosine base adjacent to guanine [4]. DNA methylation of the promoter region of a normal tumorsuppressor gene leads to the aberrant silencing of its functions. Three genes were chosen for evaluation considering their function and/or their potential role in gastric carcinogenesis: ANAPC1, CDKN2A and TP53
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