Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Urology. 2013 Feb;81(2):464.e1-9. doi: 10.1016/j.urology.2012.09.029.
To describe the establishment and characterization of a human cell line, SEM-1, from a patient diagnosed with a mediastinal seminoma.
A small percentage of germ cell tumors develop as primary lesions in extragonadal sites, and the etiology of these tumors is poorly understood. Currently, only 2 cell lines from seminoma patients have been reported, JKT-1 and TCam-2, both derived from the testis. The cell line was characterized by heterotransplantation in Nude mice, cytogenetic studies, immunohistochemical and flow cytometry staining for germ cell tumor biomarkers, quantitative reverse-transcription polymerase chain reaction for cancer testis antigen expression, and BRAF mutation screening with quantitative polymerase chain reaction.
Characterization studies confirmed the human extragonadal seminoma origin of SEM-1 and demonstrated that it had more features in common with TCam-2 than JKT-1. Specifically, SEM-1 was positive for Sal-like protein 4 (SALL-4), activator protein-2γ (AP-2γ), and cytokeratin CAM5.2, and demonstrated heterogeneous expression of stem cell markers octamer-binding transcription factor 3/4, NANOG, c-KIT, SOX17, and SOX2. Cytogenetic analysis revealed a hypotriploid chromosome number, with multiple copies of 12p, but isochromosome 12p and the BRAF mutation V600E were not identified. The cell lines also did not contain the BRD4/NUT gene rearrangement [t(15,19)] seen in midline carcinomas nor did they contain overexpressed nuclear protein in testis (NUT) genes.
SEM-1 is the first cell line derived from an extragonadal germ cell tumor showing intermediate characteristics between seminoma and nonseminoma, and as such, is an important model to study the molecular pathogenesis of this malignancy.
描述从纵隔精原细胞瘤患者中建立和鉴定的人细胞系 SEM-1。
一小部分生殖细胞肿瘤作为性腺外部位的原发性病变发展，这些肿瘤的病因尚不清楚。目前，仅报道了 2 株来自精原细胞瘤患者的细胞系，即 JKT-1 和 TCam-2，均源自睾丸。该细胞系通过 Nude 小鼠异种移植、细胞遗传学研究、用于生殖细胞肿瘤标志物的免疫组织化学和流式细胞术染色、用于癌症睾丸抗原表达的定量逆转录聚合酶链反应以及定量聚合酶链反应进行 BRAF 突变筛选进行鉴定。
鉴定研究证实 SEM-1 源自人类性腺外精原细胞瘤，并表明其与 TCam-2 的共同特征多于 JKT-1。具体而言，SEM-1 对 Sal-like 蛋白 4（SALL-4）、激活蛋白-2γ（AP-2γ）和细胞角蛋白 CAM5.2 呈阳性反应，并表现出干细胞标志物 octamer-binding transcription factor 3/4、NANOG、c-KIT、SOX17 和 SOX2 的异质性表达。细胞遗传学分析显示染色体数呈亚三倍体，12p 有多个拷贝，但未发现等臂 12p 和 BRAF 突变 V600E。这些细胞系也不包含中线癌中见到的 BRD4/NUT 基因重排[t(15,19)]，也不包含核蛋白 in testis (NUT) 基因的过表达。
SEM-1 是源自表现出精原细胞瘤和非精原细胞瘤之间中间特征的性腺外生殖细胞肿瘤的第一株细胞系，因此是研究这种恶性肿瘤分子发病机制的重要模型。
