Mosselman S, Looijenga L H, Gillis A J, van Rooijen M A, Kraft H J, van Zoelen E J, Oosterhuis J W
Department of Cell Biology, University of Nijmegen, the Netherlands.
Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2884-8. doi: 10.1073/pnas.93.7.2884.
Testicular germ cell tumors are the most common form of cancer in young adult males. They result from a derangement of primordial germ cells, and they grow out from a noninvasive carcinoma-in-situ precursor. Since carcinoma in situ can readily be cured by low-dose irradiation, there is a great incentive for non- or minimally invasive methods for detection of carcinoma in situ. We have recently shown that human Tera-2 embryonal carcinoma cells, obtained from a nonseminomatous testicular germ cell tumor, show alternative splicing and alternative promoter use of the platelet-derived growth factor alpha-receptor gene, giving rise to a unique 1.5-kb transcript. In this study we have set up a reverse transcriptase-polymerase chain reaction strategy for characterization of the various transcripts for this receptor. Using this technique, we show that a panel of 18 seminomas and II nonseminomatous testicular germ cell tumors all express the 1.5-kb transcript. In addition, a panel of 27 samples of testis parenchyma with established carcinoma in situ were all found to be positive for the 1.5-kb transcript, while parenchyma lacking carcinoma in situ, placenta, and control semen were all negative. These data show that the 1.5-kb platelet-derived growth factor alpha-receptor transcript can be used as a highly selective marker for detection of early stages of human testicular germ cell tumors.
睾丸生殖细胞肿瘤是年轻成年男性中最常见的癌症形式。它们源于原始生殖细胞的紊乱,从非侵袭性原位癌前体发展而来。由于原位癌可以通过低剂量辐射轻易治愈,因此对于检测原位癌的非侵入性或微创方法有很大的需求。我们最近发现,从非精原细胞瘤性睾丸生殖细胞肿瘤中获得的人Tera-2胚胎癌细胞,显示出血小板衍生生长因子α受体基因的可变剪接和可变启动子使用,产生了一种独特的1.5kb转录本。在本研究中,我们建立了一种逆转录酶-聚合酶链反应策略,用于表征该受体的各种转录本。使用该技术,我们发现一组18例精原细胞瘤和11例非精原细胞瘤性睾丸生殖细胞肿瘤均表达1.5kb转录本。此外,一组27例已确诊原位癌的睾丸实质样本均被发现1.5kb转录本呈阳性,而缺乏原位癌的实质、胎盘和对照精液均为阴性。这些数据表明,1.5kb血小板衍生生长因子α受体转录本可作为检测人类睾丸生殖细胞肿瘤早期阶段的高度选择性标志物。