Alterations of the 9p21 and 9q33 chromosomal bands in clinical bladder cancer specimens by fluorescence in situ hybridization.

PURPOSE To better define cytogenetic mechanisms of CDKN2 loss at 9p21 and of DBCCR1 loss at 9q33 in bladder cancer, and to determine correlation with p53 and pRb. EXPERIMENTAL DESIGN Two-color fluorescence in situ hybridization (FISH) using a chromosome 9 centromeric probe and locus-specific probes was performed. p53 and pRb were assessed by immunohistochemistry. RESULTS Thirty-seven of fifty-five (67%) samples exhibited 9p21 loss, and 32 of 44 (73%) exhibited 9q33 loss. Twelve of 43 informative samples exhibited only 9p21 loss (5 cases) or only 9q33 loss (7 cases). Homozygous deletions were noted at 9p21 and 9q33 in 31 and 14% of cases, respectively, but 9q33 homozygous deletions were generally observed in only a minor clone. There was no correlation of any chromosome 9 loss with stage, but stage did correlate with chromosome 9 ploidy status; aneusomy 9 was observed in 33% of T(a) lesions and 71% of more advanced cases (P = 0.01). Aneusomy 9 was loosely correlated with p53 abnormalities (P = 0.07), but no correlation between any chromosome 9 and pRb abnormalities was discerned. CONCLUSIONS This study strengthens the proposition that chromosome 9 losses occur early in bladder oncogenesis and before p53 alterations or development of aneusomy. The correlation of aneusomy 9 with p53 abnormalities is consistent with the presumed role of p53 in maintaining cytogenetic stability. Although the observed homozygous deletions strengthen the hypotheses that CDKN2 and DBCCR1 are important tumor suppressor genes, there is no evidence that either is a more critical or an earlier target for oncogenesis.

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