GENETIC ASPECT OF LGI CANCER

GENETIC ASPECT OF LGI CANCER


The development of colorectal cancer from normal ephithelium is a multistep process. The process had been proven to be a sequence of genetical changes including activation of protooncogens as well as inactivation of tumor suppressor genes. Numbers of these genes, which involved in complex process of colorectal tumorigenesis, are inactivation of APC gene on chromosome 5q (80% of colorectal cancer), activation of ras oncogene on chromosome 5q, 17p and 18q (50% of colon cancer), inactivation of p53 tumor suppressor gene on chromosome 17p, deleted in colon cancer (DCC) gene at chromosome 18q22 (70% of colorectal cancer) and the presence of microsatelite instability (MSI) on chromosome 2p, 2q, 3p, and 7p in Hereditary Nonpolyposis Colon Cancer (HNPCC).

A colon cancer progression model is initiated by mutation of APC gene and abnormal methylation of DNA which cause hyperproliperative epithelium followed by mutation on K-ras gene which cause the progress of the hyperproliperative epithelium to be adenoma and DC LOH and LOH on chromosome 18q which cause the progress of adenoma to be carcinoma. Finally, the mutation of p53 gene lead to the end of carcinogenesis process as invasive cancer. The model show a significant relation between molecular changes and morphological features of colorectal tomurigenesis.

(By Syarifuddin Wahid, Division of Clinical Pathology Department of Hasanuddin University of Medicines, Indonesia)