Deletion of p16 and p15 genes In schistosomiasis-associated bladder cancer (SABC).

Alterations of p16 and p15 genes have been reported in cancer cell lines and in certain malignant neoplasm. These genes are designated as candidate tumor suppressor genes because they encode proteins that function as negative cell cycle regulators at G(1)-S checkpoint. One hundred and sixty eight tumor tissue, 20 schistosomal tissue, and 50 normal tissue samples were examined. The status of p16 and p15 genes in these tissues was determined by the polymerase chain reaction and by sequencing the DNA fragments produced during PCR. In addition, the expression of p16 and p15 proteins was examined by Western blot analysis. p16 and p15 genes were detected in all normal and schistosomal tissues. Deletion of both p16 and p15 genes was observed in 72 and 36 bladder tumors, respectively. Twenty eight of the 72 cases that exhibited p16 deletions also displayed deletions of p15. Only eight cases showed loss of the p15 gene while retaining p16 gene, and p16 deletion with apparently intact p15 gene was identified in 44 cases. The present analysis also reveals that deletion in the two genes are associated with low-stage, low grade bladder cancer, schistosomiasis-associated bladder cancer (SABC) and squamous cell carcinoma type (SCC). No point mutations were identified in either gene. The expression of p16 and p15 proteins was undetectable in 75 and 38 bladder tumors, respectively, by Western blot analysis. Alteration of the p16 and p15 genes appears to be an early event in bladder cancer which occurs more frequently in SABC and SCC, and may play an important role in the development of schistosomal bladder cancer.