Li C, Larsson C, Futreal A, Lancaster J, Phelan C, Aspenblad U, Sundelin B, Liu Y, Ekman P, Auer G, Bergerheim U S
Department of Urology, Karolinska Hospital, Stockholm, Sweden.
Oncogene. 1998 Jan 29;16(4):481-7. doi: 10.1038/sj.onc.1201554.
Aberrations of 13q occur frequently in prostate cancer and this chromosome contains two known tumor suppressor genes, BRCA2 and Rb1. This study analysed 13q LOH, DNA ploidy, BRCA2 mutation and pRb expression in prostate cancers. In total, 13q deletions were found in 18 of 36 tumors but did not correlate with histological grade, stage or DNA ploidy. Two smallest regions of overlapping deletions were defined: one flanked by D13S218 and D13S153; the other flanked by D13S31 and D13S137. BRCA2 was less frequently deleted whereas Rb1 did have a high frequency of deletion. None of the two genes was located in any of these two regions. Furthermore, BRCA2 mutation was not found in the five tumors where deletions had involved the BRCA2 locus. Neither did the Rb1 deletion correlate with absent pRb expression. In addition, tetraploidy was found in 14 out of 25 tumors analysed and correlated with aberrant pRb expression. Our results indicate that 13q deletion is an early non-random event. Tumor suppressor genes other than BRCA2 or Rb1 may be the target of 13q deletions. Aberrant pRb expression may not reflect the two-hit Rb1 inactivation but may be involved in the tetraploidization of prostate cancer cells.
13号染色体长臂(13q)异常在前列腺癌中频繁出现,该染色体包含两个已知的肿瘤抑制基因,即BRCA2和Rb1。本研究分析了前列腺癌中13q杂合性缺失(LOH)、DNA倍体、BRCA2突变及磷酸化视网膜母细胞瘤蛋白(pRb)表达情况。总共在36例肿瘤中的18例发现了13q缺失,但这与组织学分级、分期或DNA倍体均无相关性。确定了两个最小的重叠缺失区域:一个位于D13S218和D13S153两侧;另一个位于D13S31和D13S137两侧。BRCA2较少发生缺失,而Rb1的缺失频率较高。这两个基因均不在这两个区域中的任何一个。此外,在涉及BRCA2基因座缺失的5例肿瘤中未发现BRCA2突变。Rb1缺失也与pRb表达缺失无关。另外,在分析的25例肿瘤中有14例发现了四倍体,且与异常pRb表达相关。我们的结果表明,13q缺失是一个早期的非随机事件。除BRCA2或Rb1之外的其他肿瘤抑制基因可能是13q缺失的靶点。异常pRb表达可能并不反映Rb1的双打击失活,但可能参与前列腺癌细胞的四倍体化过程。