Gray I C, Phillips S M, Lee S J, Neoptolemos J P, Weissenbach J, Spurr N K
Imperial Cancer Research Fund, Potters Bar, Herts, United Kingdom.
Cancer Res. 1995 Nov 1;55(21):4800-3.
Loss of the chromosomal region 10q23-25 is a frequent event in the progression of prostate adenocarcinoma. A candidate tumor suppressor gene from this region, Mxi1 at 10q25, has recently been shown to be mutated in a small number of prostate tumors. To more strictly define those regions of 10q loss that are likely to be involved in tumor advancement, we have constructed a detailed deletion map spanning 10q23-25 that incorporates Mxi1. Sixty-two % (23 of 37) of tumors analyzed exhibited some degree of 10q23-25 loss. Our data suggest the presence of a prostate tumor suppressor gene(s) near the 10q23-24 boundary, which was deleted in the overwhelming majority (22 of 23) of tumors showing loss. In contrast, specific loss of Mxi1, as opposed to loss of other 10q23-25 regions or of the entire region, was observed in only 1 of 23 tumors and was accompanied by loss of markers at the 10q23-24 boundary. Furthermore, we failed to detect any mutations in Mxi1 in those tumors showing Mxi1-associated marker loss by either single-strand conformation polymorphism analysis or direct DNA sequencing.
染色体区域10q23 - 25的缺失是前列腺腺癌进展过程中的常见事件。该区域的一个候选肿瘤抑制基因,位于10q25的Mxi1,最近已被证实在少数前列腺肿瘤中发生了突变。为了更严格地界定10q缺失中可能与肿瘤进展相关的区域,我们构建了一个包含Mxi1的跨越10q23 - 25的详细缺失图谱。在分析的37个肿瘤中,62%(23个)表现出一定程度的10q23 - 25缺失。我们的数据表明在10q23 - 24边界附近存在一个前列腺肿瘤抑制基因,在绝大多数(23个中的22个)显示缺失的肿瘤中该区域被删除。相比之下,在23个肿瘤中只有1个观察到Mxi1的特异性缺失,而非其他10q23 - 25区域或整个区域的缺失,并且伴有10q23 - 24边界处标记物的缺失。此外,通过单链构象多态性分析或直接DNA测序,我们在那些显示与Mxi1相关标记物缺失的肿瘤中未检测到Mxi1的任何突变。