12th Ljudevit Jurak International Symposium on
Comparative Pathology
June 1-2, 2001

Sanja Kapitanoviæ
Division of Molecular Medicine, Ruðer Boškoviæ Institute, Zagreb, Croatia
Molecular genetics of cancer has received large attention during the past decade. It is now quite evident that cancer is a genetic disease, caused by inherited or acquired mutations in different oncogenes  and tumour suppressor genes, and that carcinogenesis is a multi-step process. Colorectal cancer develops through a sequence of genetic alterations responsible for the progression from normal colonic mucosa to carcinoma, through the so-called “adenoma-to-carcinoma” sequence. These alterations include mutations in the K-ras oncogene and loss of heterozygosity of tumor suppressor genes such as APC, DCC and p53. Epidemiological studies have suggested that at least 15% of colorectal cancers occur in dominantly inherited patterns. The two best defined familial forms are FAP and HNPCC. In the past five years, the genetic bases for both of these syndromes have been discovered. Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disease that predisposes to colorectal cancer and is characterized by the presence of hundreds to thousands of adenomas covering the colon and rectum. If left untreated, patients have a very high risk of developing cancer during the second and third decades of life. The mutation of the tumor suppressor gene APC (adenomatous polyposis coli), discovered in 1991, was found to be the cause of FAP. At least four genes that participate in mismatch repair are implicated in the pathogenesis of the second form of hereditary colon cancer HNPCC (hereditary non-polyposis colorectal cancer): hMSH2, hMLH1, hPMS1 and hPMS2. Defective genes responsible for DNA mismatch repair (MMR) result in an increase of replicative errors at microsatellite sequences that result in insertions and deletions (microsatellite instability MS).