Mahdy E, Pan Y, Wang N, Malmström P U, Ekman P, Bergerheim U
Department of Urology, Karolinska Hospital, Stockholm, Sweden.
Anticancer Res. 2001 Sep-Oct;21(5):3167-73.
Chromosome 8 aberration and c-myc amplification have been suggested as playing important roles in the development of different human cancers. Using fluorescence in situ hybridization (FISH), chromosome 8 polysomy and c-myc amplification can be detected in cells from bladder cancer. We investigated the correlation of chromosome 8 polysomy, c-myc gene alteration and p53 deletion with histopathological parameters. Twenty-four tumors obtained from patients with bladder cancer were analyzed by interphase cytogenetics using FISH with chromosome 8 and 17 centromere probes together with an YAC clone covering the c-myc locus and three cosmid DNA probes covering the p53 locus. Chromosome 8 polysomy was found in 12 tumors. The average copy number of chromosome 8 centromere signals were significantly higher in high grade and stage, cancers. Also the c-myc copy gain and p53 deletion were significantly correlated with grade as well as stage (p<0.05, in both cases). Both polysomy 8 and c-myc copy gain were significantly correlated with p53 deletions (p<0.01) and DNA ploidy (p<0.001). On the contrary there was no significant correlation between c-myc protein over-expression and c-myc gene amplification. These results may indicate that alteration of chromosomal regions on 8q and 17p, including c-myc and p53 genes, may be linked to progression of bladder cancer.
染色体8畸变和c-myc扩增被认为在不同人类癌症的发生发展中起重要作用。使用荧光原位杂交(FISH)技术,可以在膀胱癌细胞中检测到染色体8多体性和c-myc扩增。我们研究了染色体8多体性、c-myc基因改变和p53缺失与组织病理学参数之间的相关性。使用覆盖c-myc基因座的YAC克隆和覆盖p53基因座的三个黏粒DNA探针,对24例膀胱癌患者的肿瘤进行了间期细胞遗传学分析,同时使用了染色体8和17着丝粒探针。在12个肿瘤中发现了染色体8多体性。在高级别和晚期癌症中,染色体8着丝粒信号的平均拷贝数显著更高。此外,c-myc拷贝数增加和p53缺失与分级和分期均显著相关(两种情况均为p<0.05)。8号染色体多体性和c-myc拷贝数增加均与p53缺失(p<0.01)和DNA倍体(p<0.001)显著相关。相反,c-myc蛋白过表达与c-myc基因扩增之间没有显著相关性。这些结果可能表明,包括c-myc和p53基因在内的8q和17p染色体区域的改变可能与膀胱癌的进展有关。