TP53 - Molecular Soldier’s Mutations in Bladder Cancer in the Kashmiri Population


Purpose: We made a preliminary attempt to study mutations in exons 5-8 (the DNA binding domain) ofthe tumor suppressor gene TP53, in urinary bladder cancer patients from Kashmir. Further the relation ofclinicopathological characteristics with mutation status was asessed. Materials and
Methods: The study populationconsisted 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 conformationpolymorphism (SSCP). All samples which showed different migration bands in SSCP were confirmed by DNAsequencing.
Results: 19 of 60 (31.6%) bladder cancers had mutations of the TP53 gene (11 transitions and 8transversions), three were G→A transitions, two G→T transversions, three A→C transversions, five C→Ttransitions and six A→T transversions. Predominantly missense mutations (66%) were detected but no deletionsor insertions were found. Statistically significant associations (<0.05) were noted with higher tumor stage (T2 orhigher), recurrence and large tumor size (>3cm). No correlation was found between smoking and tumor gradeand the presence of TP53 mutations.
Conclusions: Mutation of the TP53 gene is one of the commonest geneticchanges in human bladder cancer, also in a high risk ethnic Kashmiri population.