Activation of RAS family genes in urothelial carcinoma

• Published in: The Journal of urology Vol. 181; no. 5; p. 2312
• Main Authors: Boulalas, I, Zaravinos, A, Karyotis, I, Delakas, D, Spandidos, D A
• Format: Journal Article
• Language: English
• Published: United States 01.05.2009
• Subjects: Adult; Aged; Aged, 80 and over; Biopsy, Needle; Carcinoma, Transitional Cell - epidemiology; Carcinoma, Transitional Cell - genetics; Carcinoma, Transitional Cell - pathology; Case-Control Studies; Codon - genetics; DNA Mutational Analysis; DNA, Neoplasm - analysis; Female; Gene Expression Regulation, Neoplastic; Genes, ras - genetics; Genetic Predisposition to Disease - epidemiology; Humans; Immunohistochemistry; Male; Middle Aged; Multivariate Analysis; Point Mutation; Polymorphism, Restriction Fragment Length; Probability; Reverse Transcriptase Polymerase Chain Reaction; Sampling Studies; Sensitivity and Specificity; Statistics, Nonparametric; Transcriptional Activation; Urinary Bladder Neoplasms - epidemiology; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology
• ISSN: 1527-3792
• DOI: 10.1016/j.juro.2009.01.011

Bladder cancer is the fifth most common malignancy in men in Western society. We determined RAS codon 12 and 13 point mutations and evaluated mRNA expression levels in transitional cell carcinoma cases. Samples from 30 human bladder cancers and 30 normal tissues were analyzed by polymerase chain reaction/restriction fragment length polymorphism and direct sequencing to determine the occurrence of mutations in codons 12 and 13 of RAS family genes. Moreover, we used real-time reverse transcriptase-polymerase chain reaction to evaluate the expression profile of RAS genes in bladder cancer specimens compared to that in adjacent normal tissues. Overall H-RAS mutations in codon 12 were observed in 9 tumor samples (30%). Two of the 9 patients (22%) had invasive bladder cancer and 7 (77%) had noninvasive bladder cancer. One H-RAS mutation (11%) was homozygous and the remaining 89% were heterozygous. All samples were WT for K and N-RAS oncogenes. Moreover, 23 of 30 samples (77%) showed over expression in at least 1 RAS family gene compared to adjacent normal tissue. K and N-RAS had the highest levels of over expression in bladder cancer specimens (50%), whereas 27% of transitional cell carcinomas demonstrated H-RAS over expression relative to paired normal tissues. Our results underline the importance of H-RAS activation in human bladder cancer by codon 12 mutations. Moreover, they provide evidence that increased expression of all 3 RAS genes is a common event in bladder cancer that is associated with disease development.