Melamed J, Einhorn J M, Ittmann M M
Department of Pathology, New York University School of Medicine, Kaplan Cancer Center, New York, New York 10010, USA.
Clin Cancer Res. 1997 Oct;3(10):1867-72.
To clarify the role in prostate tumorigenesis played by loss of the three known or putative tumor suppressor loci on the centromeric portion of chromosome 13q, we examined 80 clinically localized and 15 advanced prostate carcinomas for allelic loss at microsatellite markers mapped to this region, including markers tightly linked to the BRCA-2, retinoblastoma (Rb), and DBM (deleted in B-cell malignancy) loci. Among the 80 clinically localized cases, 24 showed allelic loss at one or more 13q loci. In all cases with loss, the Rb and/or DBM loci were lost. No cases were found with loss of Rb without loss of DBM or loss of DBM without loss of Rb, implying a role for both the Rb and DBM loci in clinically localized prostate cancer. Loss of the BRCA-2 locus was less common (4 of 55 informative cases) and was always associated with loss of Rb and/or DBM loci. Thus, the BRCA-2 locus does not appear to play as important a role in clinically localized prostate cancer as the Rb and/or DBM loci. Allelic loss on 13q was extremely common in the clinically advanced cases; it was present in 14 of the 15 cases. The rate of allelic loss at each of the three tumor suppressor loci was increased significantly in the advanced cases (P < 0.01, Fisher's exact test). Thus, loss of heterozygosity on 13q is very common in prostate cancer and occurs at all three known or putative tumor suppressor loci on the centromeric portion of chromosome 13q.
为了阐明位于13号染色体长臂着丝粒部分的三个已知或假定的肿瘤抑制基因座缺失在前列腺肿瘤发生中的作用，我们检测了80例临床局限性前列腺癌和15例晚期前列腺癌，以观察定位于该区域的微卫星标记的等位基因缺失情况，这些标记包括与BRCA-2、视网膜母细胞瘤（Rb）和DBM（B细胞恶性肿瘤中缺失）基因座紧密连锁的标记。在80例临床局限性病例中，24例在一个或多个13q基因座出现等位基因缺失。在所有出现缺失的病例中，Rb和/或DBM基因座均缺失。未发现Rb缺失而DBM未缺失或DBM缺失而Rb未缺失的病例，这表明Rb和DBM基因座在临床局限性前列腺癌中均起作用。BRCA-2基因座的缺失较少见（55例信息性病例中有4例），且总是与Rb和/或DBM基因座的缺失相关。因此，BRCA-2基因座在临床局限性前列腺癌中似乎不如Rb和/或DBM基因座起重要作用。13q上的等位基因缺失在临床晚期病例中极为常见；15例中有14例存在。在晚期病例中，三个肿瘤抑制基因座中每个基因座的等位基因缺失率均显著增加（P<0.01，Fisher精确检验）。因此，13q上的杂合性缺失在前列腺癌中非常普遍，且发生在13号染色体长臂着丝粒部分的所有三个已知或假定的肿瘤抑制基因座上。
