Activated H-ras gene mutations in transitional cell carcinoma of urinary bladder in a Kashmiri population.

Aims And Background: The primary aim of the study was to evaluate the incidence of H-ras specific point mutations among a group of Kashmiri patients diagnosed with bladder cancer. We also explored the correlation of clinic-pathological status of the illness with these mutations.

Methods And Study Design: The DNA samples of both tumor and normal tissue were evaluated for the occurrence of H-ras activating mutations in exon 1 and 2 by PCR-SCCP and DNA sequencing. In addition, blood was also collected from all the cases to rule out any germ-line mutation.

Results: Point mutations of activated H-ras identified in bladder cancer patients were 14.5% (7 of 48), including four transversions (two G-->T and two A-->T) and three transitions (A-->G). Of the mutations, 71.4% were detected in codon 61 and 28.6% in codon 12. The pattern of mutation in the study showed a significant association with smoking in bladder tumors (P < 0.05). No correlation was found between tumor grade and/or stage and the presence of H-ras mutation.

Conclusions: Activation of H-ras by mutation plays a less frequent role than other genetic events in the development of the most transitional cell tumors of the bladder in Kashmiri population.