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(American Journal of Pathology. 2003;162:1763-1769.)
© 2003 American Society for Investigative Pathology

Short Communication

hTERT Gene Amplification and Increased mRNA Expression in Central Nervous System Embryonal Tumors

Xing Fan*, Yunyue Wang*, John Kratz*, Dan J. Brat{ddagger}, Yves Robitaille{dagger}, Albert Moghrabi{dagger}, Elizabeth J. Perlman§, Chi V. Dang*, Peter C. Burger* and Charles G. Eberhart*

From The Johns Hopkins University School of Medicine,* Baltimore, Maryland; L’hôpital Ste-Justine,{dagger} Montreal, Canada; Emory University Medical Center,{ddagger} Atlanta, Georgia; and the Children’s Memorial Hospital,§ Chicago, Illinois

High-level gains at 5p15, a chromosomal region including the human telomerase catalytic protein subunit (hTERT) gene, have been documented in several medulloblastomas. We therefore analyzed hTERT gene dosage in a group of medulloblastomas and other embryonal brain tumors using differential PCR. Amplification of the hTERT locus was detected in 15 of 36 (42%) tumors examined. To correlate gene amplification with message level, we used real-time quantitative PCR to measure hTERT mRNA in 50 embryonal brain tumors. hTERT mRNA was detected in all but one of these cases, and mRNA level correlated significantly with gene dosage (r = 0.82). Log-rank analysis of survival data revealed a trend toward poor clinical outcomes in patients with medulloblastomas containing high hTERT mRNA levels, but clinical follow-up was relatively short and the association was not statistically significant (P = 0.078). Comparative genomic hybridization was used to further analyze the tumor with the greatest hTERT gene dosage and mRNA level, a recurrent medulloepithelioma. hTERT was amplified in the recurrent tumor but not in the primary lesion, suggesting this locus can be involved in tumor progression. Our data indicate that hTERT gene amplification is relatively common in embryonal brain tumors, and that increased expression of hTERT mRNA may be associated with biologically aggressive tumor behavior.


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