Infrequent Involvement of Mutations on Neurofibromatosis Type 1 H-<i>ras</i>, K-<i>ras</i> and N-<i>ras</i> in Urothelial Tumors

Abstract

The neurofibromatosis type 1 (NF1) gene is considered a tumor-suppressor gene whose product acts upstream of ras. The ras gene is an oncogene very commonly detected in human cancers and consists of three families, H-ras, K-ras and N-ras. These genes are converted to active oncogenes by point mutations in codon 12, 13, or 61. Examination was made of the mutations of these genes in 39 urothelial malignant tumors (31 bladder cancer, 6 renal pelvic tumor, and 2 ureter tumors) using polymerase chain reaction single-stranded conformation polymorphism and direct sequencing methods. Three of 39 (7.7%) cases showed mobility shifts in the ras family gene but no point mutations in NF1 and N-ras genes could be detected. Mutations were found in 1 case in H-ras at codon 13 (GGT-GTT/GGT) and K-ras at codon 12 in 2 cases (GGT-GCT/GGT, GGT-GTT/GGT). All 3 cases had progressed far beyond grade 2 and stage pT2. It follows from the above that NF1 and ras gene mutations are infrequent in the pathogenesis of urothelial tumors.