Konishi Noboru, Nakamura Mitsutoshi, Kishi Munehiro, Ishida Eiwa, Shimada Keiji, Matsuyoshi Syuichi, Nagai Hisaki, Emi Mitsuru
Department of Pathology, Nara Medical University, Kashihara, Kashihara, Nara 634-8521, Japan.
Cancer Sci. 2003 Sep;94(9):764-8. doi: 10.1111/j.1349-7006.2003.tb01516.x.
A number of genetic events have been reported in prostate carcinogenesis, including frequent loss of heterozygosity (LOH) on chromosomes 8q, 10q, 16q and 18q. In samples of heterogeneous, multifocal prostate carcinomas, we focused on chromosome 6q using PCR-based techniques with 15 microsatellite markers to identify the specific 6q deletion within tumors. LOH of one or more polymorphic markers was detected in 10 of 21 tumors (48%). Two of these 10 tumors demonstrated LOH in all cancerous foci at specific loci and 4 tumors showed deletion in one focus. Different deletion patterns were found in 3 tumors when different polymorphic markers were used. In 90% of tumors showing LOH in one or more foci, however, two common regions of LOH were identified; one at 1.81 cM on 6q15-16.3 between markers D6S1631 and D6S1056, and the other at 5.11 cM on 6q16-21 between markers D6S424 and D6S283. By RT-PCR analysis, the TAK1 gene located at these loci did not correlate with LOH status, indicating that TAK1 is not a target gene in prostate carcinoma. The 6q deletion occurs heterogeneously and LOH was more frequent in tumors of higher pathological stages, implying that this alteration is a late event in prostate carcinogenesis. Because prostate carcinomas are genetically multicentric and of multifocal origin, it remains unclear whether the foci containing 6q deletions specifically expand within tumors or to what extent they contribute to the histological heterogeneity characteristic of the disease.
在前列腺癌发生过程中已报道了许多遗传事件，包括8号、10号、16号和18号染色体上频繁的杂合性缺失（LOH）。在异质性多灶性前列腺癌样本中，我们使用基于聚合酶链反应（PCR）的技术和15个微卫星标记聚焦于6号染色体，以识别肿瘤内特定的6号染色体缺失。在21个肿瘤中的10个（48%）检测到一个或多个多态性标记的LOH。这10个肿瘤中的2个在特定位点的所有癌灶中均显示LOH，4个肿瘤在一个灶中显示缺失。当使用不同的多态性标记时，在3个肿瘤中发现了不同的缺失模式。然而，在90%在一个或多个灶中显示LOH的肿瘤中，鉴定出两个常见的LOH区域；一个在6号染色体15 - 16.3区域6q15上标记D6S1631和D6S1056之间1.81厘摩（cM）处，另一个在6号染色体16 - 21区域6q16上标记D6S424和D6S283之间5.11 cM处。通过逆转录聚合酶链反应（RT-PCR）分析，位于这些位点的TAK1基因与LOH状态无关，表明TAK1不是前列腺癌中的靶基因。6号染色体缺失是异质性发生的，并且在病理分期较高的肿瘤中LOH更频繁，这意味着这种改变是前列腺癌发生过程中的晚期事件。由于前列腺癌在遗传上是多中心且多灶起源的，目前尚不清楚含有6号染色体缺失的灶是否在肿瘤内特异性扩展，或者它们在何种程度上导致了该疾病的组织学异质性特征。
