Purpose: We made a preliminary attempt to study mutations in exons 5-8 (the DNA binding domain) of the tumor suppressor gene TP53, in urinary bladder cancer patients from Kashmir. Further the relation of clinicopathological characteristics with mutation status was asessed.
Materials and methods: The study population consisted of 60 patients diagnosed with transitional cell carcinomas who underwent transurethral resection and /or radical cystectomy. Mutations in 5-8 exons of TP53 gene were detected by means of single strand conformation polymorphism (SSCP). All samples which showed different migration bands in SSCP were confirmed by DNA sequencing.
Results: 19 of 60 (31.6%) bladder cancers had mutations of the TP53 gene (11 transitions and 8 transversions), three were G→A transitions, two G→T transversions, three A→C transversions, five C→T transitions and six A→T transversions. Predominantly missense mutations (66%) were detected but no deletions or insertions were found. Statistically significant associations (< 0.05) were noted with higher tumor stage (T2 or higher), recurrence and large tumor size (> 3 cm). No correlation was found between smoking and tumor grade and the presence of TP53 mutations.
Conclusions: Mutation of the TP53 gene is one of the commonest genetic changes in human bladder cancer, also in a high risk ethnic Kashmiri population.