Hyytinen E R, Frierson H F, Boyd J C, Chung L W, Dong J T
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Genes Chromosomes Cancer. 1999 Jun;25(2):108-14.
Chromosome 13 is one of the most frequently altered chromosomes in cancer, including carcinoma of the prostate. Two known tumor suppressor genes, RB1 and BRCA2, map to chromosome 13; however, recent reports suggest that unknown genes on 13q are more likely to be involved in the development of prostate cancer. In order more fully to define the genetic changes on chromosome 13 in prostate neoplasms, we analyzed 27 polymorphic microsatellite markers spanning the q arm for loss of heterozygosity in 40 primary tumors and in metastases from 11 other patients who died of prostate cancer. Of the 40 primary tumors, 23 (58%) showed LOH for at least one marker. Three distinct regions at q14, q21-22, and q33, defined by markers D13S267-->D13S153, D13S166-->D13S1225, and D13S259-->D13S274, showed the most frequent LOH, suggesting their involvement in the development of prostate cancer. For the 12 patients whose tumors showed LOH at these markers, the average age at diagnosis was 58 years, which was younger than that (63 years, P < 0.05) for the 28 patients whose tumors lacked LOH. Ten of the 11 (91%) metastases showed LOH with one or more markers. Two of the three most frequently deleted regions (i.e., q14 and q21-22) in the primary tumors and markers linked to the RB1, BRCA2, and EDNRB genes showed high frequencies (56-71%) of LOH in metastases. These results demonstrate that allelic loss on chromosome 13 at q14, q21-22, and q33 occurs in a subset of primary prostate tumors and is a frequent event in metastatic lesions of prostate cancer.
13号染色体是癌症(包括前列腺癌)中最常发生改变的染色体之一。两个已知的肿瘤抑制基因RB1和BRCA2定位于13号染色体;然而,最近的报告表明,13q上的未知基因更有可能参与前列腺癌的发生发展。为了更全面地定义前列腺肿瘤中13号染色体上的基因变化,我们分析了跨越q臂的27个多态性微卫星标记,以检测40例原发性肿瘤以及11例死于前列腺癌的其他患者转移灶中的杂合性缺失情况。在40例原发性肿瘤中,23例(58%)至少有一个标记显示杂合性缺失。由标记D13S267→D13S153、D13S166→D13S1225和D13S259→D13S274定义的q14、q21 - 22和q33三个不同区域显示出最频繁的杂合性缺失,表明它们参与了前列腺癌的发生发展。对于肿瘤在这些标记处显示杂合性缺失的12例患者,诊断时的平均年龄为58岁,这比肿瘤未显示杂合性缺失的28例患者的平均年龄(63岁,P < 0.05)要小。11例转移灶中有10例(91%)显示一个或多个标记的杂合性缺失。原发性肿瘤中三个最常缺失的区域中的两个(即q14和q21 - 22)以及与RB1、BRCA2和EDNRB基因相关的标记在转移灶中显示出高频率(56 - 71%)的杂合性缺失。这些结果表明,13号染色体q14、q21 - 22和q33处的等位基因缺失发生在一部分原发性前列腺肿瘤中,并且在前列腺癌转移灶中是常见事件。