Estudio de patrones de metilación génica en tumores del tubo digestivo / Gene methylation patterns in digestive tumors

ABSTRACT

Background: The loss of tumor suppresor 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. Aim: To study the methylation pattern of a group of genes in biopsy samples of gastrointestinal tumors. Material and methods: 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. Results: The general methylation frequency of CDH1, FHIT, CDKN2A, APC and MLH1 genes was 64.1, 56, 39.8, 18.1 and 34 percent 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 ¡ess 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. Conclusions: 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.