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JNCI Journal of the National Cancer Institute 1999 91(15):1321-1326; doi:10.1093/jnci/91.15.1321
© 1999 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 91, No. 15, 1321-1326, August 4, 1999
© 1999 Oxford University Press

REPORTS

Telomerase Activity in Germ Cell Cancers and Mature Teratomas

Juan Albanell, George J. Bosl, Victor E. Reuter, Monika Engelhardt, Sonia Franco, Malcolm A. S. Moore, Ethan Dmitrovsky

Affiliations of authors: J. Albanell, M. Engelhardt, M. A. S. Moore, Laboratory of Developmental Hematopoiesis, Cell Biology Program, Sloan-Kettering Institute, New York, NY; G. J. Bosl (Department of Medicine), V. E. Reuter (Department of Pathology), Memorial Hospital, Memorial Sloan-Kettering Cancer Center, New York, NY; S. Franco, Laboratory of Developmental Hematopoiesis, Cell Biology Program, Sloan-Kettering Institute, and Department of Pediatrics, Memorial Hospital, Memorial Sloan-Kettering Cancer Center; E. Dmitrovsky, Laboratory of Molecular Medicine, Molecular Pharmacology and Therapeutics Program, Sloan-Kettering Institute, and Department of Medicine, Memorial Hospital, Memorial Sloan-Kettering Cancer Center.

Correspondence to: Ethan Dmitrovsky, M.D., Remsen 7650, Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755-3835 (e-mail: ethan.dmitrovsky{at} dartmouth.edu).

BACKGROUND: An inverse relationship has been reported between the presence of telomerase enzymatic activity and the induction of differentiation in human tumor cell lines. Male germ cell tumors represent an attractive clinical model to assess this relationship further because high telomerase activity is present in normal germ cell progenitors and in embryonal carcinomas that can differentiate into mature teratomas. To investigate how telomerase activity and the differentiation state of germ cell tumors are related, telomerase activities and telomere lengths were measured in benign testicular tissues, germ cell cancers, and mature or immature teratomas. METHODS: By use of a modified telomeric repeat amplification protocol (TRAP) assay, telomerase activity was measured in four specimens of benign testicular tissue, in 27 germ cell cancers, in seven mature teratomas, and in one immature teratoma. Telomere lengths were measured in all specimens by restriction digestion of genomic DNA and Southern blot hybridization analysis. Associations between telomerase activity and tissue histopathology were assessed with two-sided Fisher's exact tests. RESULTS: Telomerase activity was detected in all examined germ cell cancers and in the benign testicular tissue specimens. In marked contrast, telomerase activity was not detected in any mature teratoma (P<.0001). Very long telomeres were detected in some mature teratomas, consistent with telomerase repression as a late event in teratoma formation. The immature teratoma, with malignant transformation, had high telomerase activity. CONCLUSION: Telomerase is active in germ cell cancers and repressed in mature teratomas. The absence of telomerase activity may contribute to the limited proliferative capacity of mature teratomas. These findings support the existence of an inverse relationship between telomerase activity and the differentiation state of clinical germ cell tumors.


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