ACTIVATING MUTATIONS IN THE K-RAS GENE IN ULCERATIVE-COLITIS AND CROHNS-DISEASE

Patients with ulcerative colitis (UC) and Crohn's disease have an increased risk for developing cancer of the colon. Mutations in the K-ras gene are relatively frequent in specimens from patients with sporadic colon cancer, but less frequent in cases of cancer complicating ulcerative colitis. In order to study the problem further we used the polymerase chain reaction (PCR) technique followed by a restriction fragment length polymorphism (RFLP) assay, to detect mutations at codon 12 of K-ras in biopsy specimens from patients with UC or Crohn's disease. Six among 27 patients (22.2%) with UC and 2 of the 19 patients (10.5%) with Crohn's disease examined, carried a mutation at codon 12 of K-ras. Our results indicate that mutations in K-ras may be a genetic marker that would reveal the predisposition to colon cancer among this group of patients. alterations are related to the pathogenesis of invasive carcinoma in patients with UC or Crohn's disease and map the preneoplastic cells in the area of the dysplasia. K-ras, H-ras and N-ras oncogenes are members of the ras family of genes. The three genes code for structurally and immunologically related proteins of 21 kD, known as ras p21. ras p21 is located on the inner side of the plasma membrane, possesses GTPse activity and is involved in a signal transduction pathway (4). Transforming mutations in ras genes are found in about 50% of the human epithelial neoplasms and they have a crucial role in the progression of the malignancy. K-ras mutations are relatively frequent in colon cancer and in UC and Crohn's disease they have been reported to exist in various frequencies (5-7). The aim of the present study was to determine whether K-ras mutations play a role in the pathogenesis of invasive carcinoma in UC and Crohn's disease. We detected K-ras mutations at codon 12 in 22.2% of patients with UC and 10.5% in patients with Crohn's disease.