Macoska Jill A, Paris Pamela, Collins Colin, Andaya Armann, Beheshti Ben, Chaib Hassan, Kant Rajiv, Begley Lesa, MacDonald James W, Squire Jeremy A
Department of Urology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0944, USA.
Cancer Genet Cytogenet. 2004 Oct 1;154(1):36-43. doi: 10.1016/j.cancergencyto.2004.02.013.
Deletion or rearrangement of sequences that map to the short arm of chromosome 8 (8p) are frequently associated with human prostate tumorigenesis. These losses often involve the entire short arm of chromosome 8 or very large regions of distal or proximal 8p, and several putative tumor suppressor genes mapping to 8p have been described. However, the mechanism responsible for 8p loss during prostate tumorigenesis has not been elucidated. In this study, we report data obtained using array comparative genomic hybridization and spectral karyotyping, which demonstrate successive translocation and deletion events responsible for loss of one copy of 8p in transformed human prostate epithelial cells. Moreover, this loss was accompanied by a pronounced transcriptional downregulation of genes mapping to the remaining copy of 8p and enhanced expression of traits associated with neoplastic transformation. Taken together, these studies illustrate a potential mechanism and functional role for 8p loss in human prostate tumorigenesis.
定位于8号染色体短臂(8p)的序列缺失或重排常与人类前列腺肿瘤发生相关。这些缺失通常涉及8号染色体的整个短臂或8p远端或近端的非常大的区域,并且已经描述了几个定位于8p的假定肿瘤抑制基因。然而,前列腺肿瘤发生过程中8p缺失的机制尚未阐明。在本研究中,我们报告了使用阵列比较基因组杂交和光谱核型分析获得的数据,这些数据表明在转化的人前列腺上皮细胞中,连续的易位和缺失事件导致8p的一个拷贝丢失。此外,这种丢失伴随着定位于8p剩余拷贝的基因明显的转录下调以及与肿瘤转化相关特征的表达增强。综上所述,这些研究阐明了8p缺失在人类前列腺肿瘤发生中的潜在机制和功能作用。