NONRANDOM CHROMOSOMAL CHANGES IN TRANSITIONAL CELL-CARCINOMA OF THE BLADDER

Abstract

Nine cases of transitional cell carcinoma (8 from the urinary bladder and 1 from the ureter; 6 noninvasive and 3 invasive) were subjected to detailed cytogenetic analysis with a G-banding method. The synchronization of primary cultures with methotrexate for high-resolution banding was performed in 5 cases. In the remaining 4 cases, the chromosomes were obtained from short-term cultures after prolonged (16 h) exposure to Colcemid. Two cases were near-tetraploid, 1 was hypotriploid, and 6 were near-diploid (3 hyperdiploid and 3 hypodiploid). All but 1 case showed various structural abnormalities in the karyotype. The chromosomal changes ranged from the presence of only 2 abnormal chromosomes (markers) to complex karyotypes with as many as 15 markers. In most tumors, the origin of the marker chromosomes could be readily deciphered. The nonrandom chromosomal aberrations included: an isochromosome of the short arm of chromosome 5 (3 cases); monosomy of chromosome 9 found in 4 cases (this was the sole abnormality in 1 case); involvement of chromosome 8 as an isochromosome of the long arm (2 cases) or loss of the short arm due to deletion (1 case) or translocation (1 case); and interstitial deletion of chromosome 13 (3 cases). The formation of i(5p) and monosomy 9 may be the primary karyotypic changes in 2 subgroups of transitional cell carcinoma. Involvement of chromosomes 8 and 13 seems to be a result of secondary karyotypic evolution. Two invasive tumors showed the presence of secondary clones, with additional structural chromosome aberrations superimposed on those already existing in the main cell population. In both cases, the additional aberrations involved the short arm of chromosome 11, resulting in loss of genetic material from the short arm. The short arm of chromosome 11 is the putative site of an oncogene which has been isolated from human bladder carcinoma cell lines. Deletion of the 11p was also seen in 1 case of noninvasive transitional cell carcinoma localized in the ureter; the material from 11p was probably translocated to chromosome 13. The loss of genetic material from the short arm of chromosome 11 is a secondary event in the karyotypic evolution of transitional cell carcinoma, probably related to the invasive behavior of the tumor.