scholarly journals Differentiation-Dependent Regulation of Human Endogenous Retrovirus K Sequences and Neighboring Genes in Germ Cell Tumor Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Thomas Mueller ◽  
Claudia Hantsch ◽  
Ines Volkmer ◽  
Martin S. Staege
2008 ◽  
Vol 82 (20) ◽  
pp. 10008-10016 ◽  
Author(s):  
Klemens Ruprecht ◽  
Humberto Ferreira ◽  
Aline Flockerzi ◽  
Silke Wahl ◽  
Marlies Sauter ◽  
...  

ABSTRACT The human germ cell tumor line Tera-1 produces retroviral particles which are encoded by the human endogenous retrovirus family HERV-K(HML-2). We show here, by quantitative reverse transcriptase PCR, that HML-2 gag and env RNA transcripts are selectively packaged into Tera-1 retroviral particles, whereas RNAs from cellular housekeeping genes and from other HERV families (HERV-H and HERV-W) are nonselectively copackaged. Assignment of cloned HML-2 gag and env cDNAs from Tera-1 retroviral particles to individual HML-2 loci in the human genome demonstrated that HML-2 RNA transcripts packaged into Tera-1 retroviral particles originate almost exclusively from an HML-2 provirus on chromosome 22q11.21. Based on relative cloning frequencies, this provirus was the most active among a total of eight transcribed HML-2 loci identified in Tera-1 cells. These data suggest that at least one HML-2 element, that is, the HML-2 provirus on 22q11.21, has retained the capacity for packaging RNA into HML-2-encoded retroviral particles. Given its elevated transcriptional activity and the presence of a full-length Gag open reading frame, the 22q11.21 HML-2 provirus may also significantly contribute to Gag protein and thus particle production in Tera-1 cells. Our findings provide important clues to the generation and biological properties of HML-2-encoded particles. In addition, copackaging of non-HML-2 HERV transcripts in HML-2-encoded particles should inform the debate about endogenous retroviral particles putatively encoded by non-HML-2 HERV families that have previously been described for other human diseases, such as multiple sclerosis.


1992 ◽  
Vol 25 (5) ◽  
pp. 563-576 ◽  
Author(s):  
JUN-ICHI HATA ◽  
JUNICHIRO FUJIMOTO ◽  
EIZABURO ISHII ◽  
AKIHIRO UMEZAWA ◽  
YASUO KOKAI ◽  
...  

2001 ◽  
Vol 19 (12) ◽  
pp. 3029-3036 ◽  
Author(s):  
C. Bokemeyer ◽  
A. J.M. Gillis ◽  
K. Pompe ◽  
F. Mayer ◽  
B. Metzner ◽  
...  

PURPOSE: High-dose chemotherapy (HD-Ctx) followed by autologous peripheral-blood stem-cell (PBSC) transplantation is currently investigated in patients with poor prognosis or relapsed metastatic germ cell tumor (GCTs). This study analyzed the presence and the clinical importance of contaminating tumor cells in PBSC preparations used to support HD-Ctx in GCT patients. PATIENTS AND METHODS: Seven targets for reverse transcription polymerase chain reaction (RT-PCR)-based detection of GCT cells were able to detect seminomatous and different histologic variants of nonseminomatous tumor cells. PBSC preparations from 57 patients were investigated for the presence of contaminating tumor cells using this set of targets, including beta human chorionic gonadotropin (β-hCG), fibronectin (EDB variant), epidermal growth factor receptor (EGFR), CD44 (v8 to 10 variant), germ cell and placental alkaline phosphatase (AP), human endogenous retrovirus type K (ENV and GAG), and XIST. Samples of PBSC preparations from four healthy donors for allogenic transplantations as well as blood specimens from 10 healthy volunteers served as negative controls. RESULTS: Fifty patients (43 first-line and seven second-line Ctx) were assessable. Combining all RT-PCR results, 29 PBSC preparations (58%) were positive for tumor-specific amplification products (HERV-K 0, fibronectin 4, XIST 14, β-hCG 19, AP 19, CD44 24, EGFR 26). Ten (35%) of 29 patients who underwent transplantation with positive PBSC preparations and seven (33%) of 21 patients with negative PBSC preparations have suffered relapse or progression (not significant [ns]). With a median follow-up of 22 months (2 to 66) post–HD-Ctx projected 3-year survival rates are 68% (RT-PCR+) and 58% (RT-PCR−) (ns). None of the 10 control peripheral-blood samples showed positivity for any of the targets studied. CONCLUSION: GCT cells can be detected in more than 50% of PBSC preparations using a RT-PCR approach with multiple targets. Despite the presence of tumor cells, retransplantation of the PBSC products did not effect long-term outcome. Factors such as responsiveness to chemotherapy and tumor mass seem to overcome the importance of potentially re-infused tumor cells.


2012 ◽  
Vol 51 (7) ◽  
pp. 717-726 ◽  
Author(s):  
Daniel Nettersheim ◽  
Birgit Westernströer ◽  
Natalie Haas ◽  
Anke Leinhaas ◽  
Oliver Brüstle ◽  
...  

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