Telomerase activity and oncogenesis in giant cell tumor of bone.
BACKGROUND
Benign giant cell tumor of bone (GCT) is a primary skeletal neoplasm with an unpredictable pattern of biologic aggressiveness and cytogenetic findings characterized by telomeric associations and telomeric reduction. The role of maintaining telomeric integrity is performed by telomerase. To determine if telomerase activity is present, cell extracts from fibroblasts and tumor cells from five patients with GCT were analyzed and compared with HeLa (a positive control cell line).


METHODS
Telomerase activity was detected by visualizing the extension of radioactive telomeric repeats on DNA sequencing gels. Telomere reduction was assessed using southern blot analyses of the restriction enzyme Hinf I digested DNA with a radio-labeled telomere probe.


RESULTS
Telomerase or telomerase-like activity was detected in the cell extracts from HeLa and tumor cells. However, GCT telomerase activity varied and was less than that observed in HeLa, but no activity was detected from fibroblasts. In addition, telomere reduction was seen in DNA isolated from both HeLa and GCT but not in fibroblasts or age-matched controls.


CONCLUSIONS
Telomere reduction and telomerase activity may be oncogenic sustaining events required to maintain the transformed phenotype seen in GCT.
Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2550.
H S
HS
Schwartz
S F
SF
Juliao
M F
MF
Sciadini
L K
LK
Miller
M G
MG
Butler
D000328:Adult; D001345:Autoradiography; D015139:Blotting, Southern; D001859:Bone Neoplasms / Q000201:enzymology*; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000201:enzymology*; D006801:Humans; D008297:Male
D004273:DNA, Neoplasm; D004253:DNA Nucleotidylexotransferase