title: Establishment and characterization of a new human extragonadal germ cell line, SEM-1, and its comparison with TCam-2 and JKT-1.
abstract: OBJECTIVE
  To describe the establishment and characterization of a human cell line, SEM-1, from a patient diagnosed with a mediastinal seminoma.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
authors: Sarah M
authors: SM
authors: Russell
authors: Melissa G
authors: MG
authors: Lechner
authors: Anusuya
authors: A
authors: Mokashi
authors: Carolina
authors: C
authors: Megiel
authors: Julie K
authors: JK
authors: Jang
authors: Clive R
authors: CR
authors: Taylor
authors: Leendert H J
authors: LH
authors: Looijenga
authors: Christopher A
authors: CA
authors: French
authors: Alan L
authors: AL
authors: Epstein
mesh_terms: D000782:Aneuploidy; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000378:metabolism* / Q000473:pathology; D004252:DNA Mutational Analysis; D015870:Gene Expression; D015321:Gene Rearrangement; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000235:genetics; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D055760:SOXF Transcription Factors / Q000378:metabolism; D018239:Seminoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; C400901:CAM 5.2 antigen; D018398:Homeodomain Proteins; C486780:NANOG protein, human; C000630260:NUTM1 protein, human; D000071317:Nanog Homeobox Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; D015513:Oncogene Proteins; D012333:RNA, Messenger; C472575:SALL4 protein, human; C109188:SOX17 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D055760:SOXF Transcription Factors; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D007633:Keratins; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
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