hTERT gene amplification and increased mRNA expression in central nervous system embryonal tumors.
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.
Fan
Xing
X
Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Wang
Yunyue
Y
Kratz
John
J
Brat
Dan J
DJ
Robitaille
Yves
Y
Moghrabi
Albert
A
Perlman
Elizabeth J
EJ
Dang
Chi V
CV
Burger
Peter C
PC
Eberhart
Charles G
CG
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000235:genetics / Q000473:pathology*; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins; D005260:Female; D005784:Gene Amplification; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000473:pathology*; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics / Q000473:pathology; D009693:Nucleic Acid Hybridization / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D019098:Telomerase / Q000235:genetics*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase