Strohmeyer D, Langenhof S, Ackermann R, Hartmann M, Strohmeyer T, Schmidt B
Department of Urology, Heinrich-Heine-University, Düsseldorf, Germany.
J Urol. 1997 May;157(5):1973-6.
Inactivation of the DCC (Deleted in Colon Carcinoma) tumor suppressor gene by allelic loss and/or reduced expression is associated with the development of colon cancer, gliomas, gastric and prostatic malignancies. In a total cohort of 51 testicular germ cell tumors (GCT) of different histologies we analyzed restriction fragment length polymorphism (RFLP) for DCC at two specific DNA sites in 37 GCT and DCC mRNA expression compared to that of the adjacent normal testicular tissue in 41 GCT, one Leydig cell tumor and one testicular metastasis of a non-small cell lung cancer (NSCLC). Two of 17 tumors (11.7%) informative for the Msp I polymorphic site of the DCC gene and 6/25 tumors (24.0%) informative for variable number of tandem repeat (VNTR) showed loss of heterozygosity (LOH). DCC expression was analyzed by semi-quantitative polymerase chain reaction after initial reverse transcription (RT-PCR). Thirty of 41 GCT (73.1%) and both, the Leydig cell tumor and the testicular metastasis of NSCLC, had a nearly complete or total loss of DCC mRNA expression. Six of 11 (54.5%) seminomas and 24/30 (80.0%) nonseminomas had this loss of expression. Twelve of 17 (70.5%) localized tumors, 9/13 (69.2%) tumors with lymph node involvement and 9/11 (82.2%) tumors with distant metastases showed decreased or absent DCC expression. This data suggests that inactivation of the DCC gene, especially the loss of DCC expression, is associated with the development and progression of human GCT.
通过等位基因缺失和/或表达降低使结肠癌缺失基因（DCC）肿瘤抑制基因失活，与结肠癌、神经胶质瘤、胃癌和前列腺恶性肿瘤的发生发展相关。在总共51例不同组织学类型的睾丸生殖细胞肿瘤（GCT）队列中，我们分析了37例GCT中DCC在两个特定DNA位点的限制性片段长度多态性（RFLP），并比较了41例GCT、1例间质细胞瘤和1例非小细胞肺癌（NSCLC）睾丸转移瘤中DCC mRNA表达与相邻正常睾丸组织的DCC mRNA表达。在17例对DCC基因的Msp I多态性位点具有信息价值的肿瘤中，有2例（11.7%）显示杂合性缺失（LOH）；在25例对可变串联重复序列（VNTR）具有信息价值的肿瘤中，有6例（24.0%）显示杂合性缺失。通过初始逆转录后的半定量聚合酶链反应（RT-PCR）分析DCC表达。41例GCT中有30例（73.1%）以及间质细胞瘤和NSCLC睾丸转移瘤均几乎完全或完全丧失DCC mRNA表达。11例精原细胞瘤中有6例（54.5%）以及30例非精原细胞瘤中有24例（80.0%）出现这种表达缺失。17例局限性肿瘤中有12例（70.5%）、13例有淋巴结受累的肿瘤中有9例（69.2%）以及11例有远处转移的肿瘤中有9例（82.2%）显示DCC表达降低或缺失。这些数据表明，DCC基因的失活，尤其是DCC表达的缺失，与人GCT的发生发展相关。
