Abstract
The loss of tumor suppressor gene function damages the defensive mechanisms that protect the indemnity of genetic material. Promoter gene methylation is one of the inactivation mechanisms of suppressor genes.To study the methylation pattern of a group of genes in biopsy samples of gastrointestinal tumors.Forty eight gastric, 25 gallbladder, 24 colon and 6 pancreas cancer biopsy samples were randomly selected. The methylation pattern of CDH1, FHIT, CDKN2A, APC and MLH1 genes, was studied using a specific polymerase chain reaction test for methylation. Demographic, morphological and follow up variables of patients bearing the tumors were also analyzed.The general methylation frequency of CDH1, FHIT, CDKN2A, APC and MLH1 genes was 64.1, 56, 39.8, 18.1 and 34% respectively. In gastric cancer samples there was a correlation between APC gene methylation and well differentiated tumors; between CDH1 methylation and Lauren diffuse type and the presence of three or more metastasic lymph nodes; between FHIT, CDKN2A and CDH1 gene methylation and male gender. In less differentiated gallbladder tumors, the frequency of CDH1 methylation was higher. There was a tendency towards a lower survival in colon and gastric cancer when MLH1 (p =0.07) y CDKN2A (p= 0.06) were methylated, respectively.An abnormal methylation pattern was associated with morphological features in gastric and gallbladder cancer and with a tendency towards a lower survival in colon and gastric cancer.
Highlights
The loss of tumor suppresor gene function damages the defensive mechanisms that protect the indemnity of genetic material
Analizar el patrón de metilación de importantes genes involucrados en la carcinogénesis en pacientes con carcinomas del tubo digestivo, relacionando tales alteraciones con sus alteraciones morfológicas y el comportamiento biológico de la neoplasia
Prognostic analysis of E-cadherin gene promoter hypermethylation in patients with surgically resected, node-positive, diffuse gastric cancer
Summary
The loss of tumor suppresor gene function damages the defensive mechanisms that protect the indemnity of genetic material. Se seleccionó genes supresores de tumores de diferentes vías metabólicas relacionados con el ciclo celular FHIT (Fragile Histidine Triad), CDKN2A (p16) y APC (Adenomatous Poliposis Coli), el gen MLH1 (Human Mut Homologue 1) probablemente el más importante de los genes reparadores de ADN genómico, relacionado con inestabilidad microsatelital y el gen CDH1 (Caderina E), que codifica una proteína de transmembrana que participa en el complejo de moléculas de adhesión involucrada en la metástasis e invasión tumoral[9,10,25]. Analizar el patrón de metilación de importantes genes involucrados en la carcinogénesis en pacientes con carcinomas del tubo digestivo, relacionando tales alteraciones con sus alteraciones morfológicas y el comportamiento biológico de la neoplasia
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