Interrelationships among chromosome aneuploidy, promoter hypermethylation, and protein expression of the CDKN2A gene in individuals from northern Brazil with gastric adenocarcinoma.
Numerical alterations of chromosome 9, the status of promoter methylation and protein expression of the CDKN2A gene (aliases include p16 and p16(INK4a)), the possible association with gain of chromosome X, and the interrelation of these findings with clinic and pathological characteristics were investigated in gastric adenocarcinomas. Fluorescence in situ hybridization analysis with centromeric DNA probes, immunohistochemical staining, and methylation-specific polymerase chain reaction assays were performed in 15 gastric adenocarcinomas samples from individuals from northern Brazil. Aneuploidies of chromosomes X and 9 were found in all samples, both intestinal and diffuse type. Monosomy of chromosome 9 and gain of a copy of chromosome X (in both sexes) were observed in 100% of cases. Hypermethylation frequency and protein expression of CDKN2A were also found in all cases analyzed. No association of genetic and epigenetic alterations with histological type, tumor aggressiveness, and invasion was found (P > 0.05), which may be attributable to small sample size. There was a high level of association between absence of p16 protein expression levels, CDKN2A gene promote hypermethylation, and chromosome 9 aneuploidy (100% of cases). Thus, in the present samples, the apparent mechanisms behind p16 silencing include loss of chromosome 9 and promoter region hypermethylation.
Guimarães
Adriana Costa
AC
Human Cytogenetics and Toxicological Genetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Campus Universitário do Guamá, Av. Augusto Correa, 01, CEP 66075-900, Belém, PA, Brazil.
Lima
Eleonidas Moura
EM
Khayat
André Salim
AS
Girão Faria
Mário Henrique
MH
Barem Rabenhorst
Silvia Helena
SH
Pitombeira
Márcia Valéria
MV
Assumpção
Paulo Pimentel
PP
de Oliveira Bahia
Marcelo
M
Lima de Lima
Patrícia Danielle
PD
de Arruda Cardoso Smith
Marília
M
Burbano
Rommel Rodríguez
RR
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D002899:Chromosomes, Human, Pair 9; D041321:Chromosomes, Human, X; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D019941:Cyclin-Dependent Kinase Inhibitor p16