The differentiation status of primary gonadal germ cell tumors correlates inversely with telomerase activity and the expression level of the gene encoding the catalytic subunit of telomerase.
BACKGROUND
The activity of the ribonucleoprotein enzyme telomerase is detectable in germ, stem and tumor cells. One major component of telomerase is human telomerase reverse transcriptase (hTERT), which encodes the catalytic subunit of telomerase. Here we investigate the correlation of telomerase activity and hTERT gene expression and the differentiation status of primary testicular germ cell tumors (TGCT).


METHODS
Telomerase activity (TA) was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by online RT-PCR in 42 primary testicular germ cell tumors. The control group consisted of benign testicular biopsies from infertile patients.


RESULTS
High levels of telomerase activity and hTERT expression were detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content. In contrast, differentiated teratomas and testicular control tissue without germ cells (Sertoli-cell-only syndrome) showed no telomerase activity and only minimal hTERT expression.


CONCLUSIONS
These findings demonstrate an inverse relationship between the level of telomerase activity and hTERT mRNA expression and the differentiation state of germ cell tumors. Quantification of telomerase activity and hTERT mRNA expression enables a new molecular-diagnostic subclassification of germ cell tumors that describes their proliferation potential and differentiation status.
Schrader
Mark
M
Department of Urology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. schrader@medizin.fu-berlin.ded
Burger
Angelika M
AM
Müller
Markus
M
Krause
Hans
H
Straub
Bernd
B
Schostak
Martin
M
Schulze
Wolfgang
W
Lauke
Heidrun
H
Miller
Kurt
K
D020134:Catalytic Domain / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D018237:Germinoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase