Washburn J G, Wojno K J, Dey J, Powell I J, Macoska J A
Department of Surgery, The University of Michigan, Ann Arbor 48109-0946, USA.
Clin Cancer Res. 2000 Dec;6(12):4647-52.
Deletions of chromosome sequences mapping to the short arm of chromosome 8 have been observed frequently in a variety of human cancers. A small number of studies have suggested that the terminal portion of the short arm of chromosome 8, 8pter-p23, may be deleted independently of other portions of 8p in human tumors, and that deletion of the 8pter-p23 region may be correlated with poor prognosis. The aim of the present study was to physically define the minimal region of 8pter-p23 deletion and to define the frequency and prognostic significance of 8pter-p23 loss in human prostate tumors. DNA was purified from normal and tumor tissues of 45 radical prostatectomy specimens and amplified for 15 highly polymorphic microsatellite sequences, 13 spanning 8pter-p23 and 2 proximal 8p markers. Allelic loss of 8p sequences was observed in 28 of 45 (62%) tumors examined. Of these, approximately half (12 of 28; 43%) demonstrated independent loss of the 8pter-p23 region, with several tumors defining a 5-cM minimal region of deletion spanning D8S264-D8S1824-D8S1781-D8S262-D8S1798. When serum prostate-specific antigen was used as a surrogate end point marker for survival, 8pter-p23 loss was significantly associated with reduced disease-free progression (log-rank P = 0.0426). Moreover, loss of the 8pter-p23 region was significantly associated with poor survival for American Caucasian (log-rank P = 0.0024) but not African-American (log-rank P = 0.5832) prostate cancer patients. These studies suggest that independent deletion of 8pter-p23 is differentially associated with disease recurrence and poor outcome in American Caucasian but not African-American prostate cancer patients.
在多种人类癌症中,经常观察到染色体序列缺失定位于8号染色体短臂。少数研究表明,8号染色体短臂的末端部分,即8pter-p23,在人类肿瘤中可能独立于8p的其他部分发生缺失,并且8pter-p23区域的缺失可能与预后不良相关。本研究的目的是从物理上确定8pter-p23缺失的最小区域,并确定8pter-p23缺失在人类前列腺肿瘤中的频率和预后意义。从45例根治性前列腺切除术标本的正常和肿瘤组织中纯化DNA,并对15个高度多态性微卫星序列进行扩增,其中13个跨越8pter-p23,2个为8p近端标记。在45个检测的肿瘤中有28个(62%)观察到8p序列的等位基因缺失。其中,约一半(28个中的12个;43%)显示8pter-p23区域独立缺失,有几个肿瘤确定了一个5厘摩的最小缺失区域,跨越D8S264-D8S1824-D8S1781-D8S262-D8S1798。当血清前列腺特异性抗原用作生存的替代终点标志物时,8pter-p23缺失与无疾病进展显著相关(对数秩检验P = 0.0426)。此外,8pter-p23区域的缺失与美国白人前列腺癌患者的不良生存显著相关(对数秩检验P = 0.0024),但与非裔美国前列腺癌患者无关(对数秩检验P = 0.5832)。这些研究表明,8pter-p23的独立缺失与美国白人而非非裔美国前列腺癌患者的疾病复发和不良结局存在差异关联。