Over-expression and amplification of the c-myc gene in human urothelial carcinoma

To understand the mechanisms underlying increased expression of Myc protein in human urinary bladder cancer, expression of c-myc mRNA and the copy num ber of the c-myc gene were determined. Expression of mRNA was measured by q uantitative RT-PCR in 40 urothelial carcinomas and in 18 histologically nor mal mucosae. Mean expression in tumors was significantly increased (3.23 +/ - 2.63 AU vs. 1.90 +/- 0.95 AU, p < 0.023) and exceeded the highest level i n normal mucosa in 15 (37.5%) tumors. The c-myc gene copy number was higher than in leukocytes and normal bladder mucosa in 14 of 40 tumors, but only 3 among these showed a more than I-fold increase indicative of gene amplifi cation. Most, but not all, tumors with elevated expression displayed an inc reased gene copy number (p < 0.0001). In line with other studies of the pro tein level, no significant association either of c-myc mRNA over-expression or of increased gene copy number with tumor stage or grade was observed. T he data indicate that elevated mRNA expression as a consequence of increase s in c-myc gene copy number often underlies Myc protein overexpression in b ladder cancer. This increase may be a consequence of, most frequently, chro mosome 8q gain and, occasionally, gene amplification, while in some tumors deregulation of mRNA expression occurs without evident changes in the c-myc gene copy number. Int. J. Cancer (Pred. Oncol.) 84:169-173, 1999. (C) 1999 Wiley-Liss, Inc.