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- Title
Differentiating Alternative Splice Variant Patterns of Human Telomerase Reverse Transcriptase in Thyroid Neoplasms.
- Authors
Yongchun Wang; Jeanne Kowalski; Hua-Ling Tsai; Radharani Marik; Nijaguna Prasad; Helina Somervell; Pang-Kuo Lo; Lauren E. Sangenario; Lars Dyrskjot; Torben F. Orntoft; William H. Westra; Alan K. Meeker; James R. Eshleman; Christopher B. Umbricht; Martha A. Zeiger
- Abstract
Background:Although fine-needle aspiration (FNA) biopsy of thyroid nodules is very sensitive in detecting thyroid malignancy, it remains ambiguous in 20â30 of cases. Current biomarkers for thyroid cancer lack either the sensitivity or specificity to substantially address this clinical problem. The aim of this study was to investigate the gene expression patterns of human telomerase reverse transcriptase (hTERT) alternative splice variants in benign and malignant thyroid tumors in an attempt to find a more reliable biomarker in the differential diagnosis of thyroid nodules.Methods:One hundred and thirty-three thyroid tumors from eight histopathological tumor types were collected from patients undergoing thyroid surgery at Johns Hopkins Hospital. Gene expression patterns of hTERTalternative splice variants were investigated in the tumors by nested reverse transcriptase-PCR. Telomerase enzyme activity was evaluated in a subset of 16 samples associated with the different hTERTpatterns. Association of c-mycexpression and hTERTpatterns was also examined.Results:Malignant thyroid tumors exhibited a greater proportion of the active full-length hTERTtranscript (0.57 ± 0.15) than inactive splice variants, αâ(0.13 ± 0.02), or βâ/αâβâdeletion transcripts (0.30 ± 0.11; p< 0.001). The opposite was observed in benign tumors, which exhibited greater proportions of βâ/αâβâdeletion transcripts (0.64 ± 0.08) than either the full-length (0.19 ± 0.06) or αâdeletion transcripts (0.17 ± 0.02; p< 0.001). Similar results were observed among a diagnostically challenging subset of 50 thyroid tumors that were suspicious for malignancy on FNA. Further, increased telomerase enzymatic activity was only associated with expression of the full-length hTERTisoform. In contrast, c-mycexpression, which has been implicated in hTERTregulation, correlated with overall hTERTtranscription without specificity for expression of the full-length isoform.Conclusions:These differences in gene expression patterns of hTERTalternative splice variants may provide a useful adjunct to FNA diagnosis of suspicious thyroid tumors.
- Subjects
THYROID cancer; CANCER diagnosis; TELOMERASE; DNA polymerases
- Publication
Thyroid, 2008, Vol 18, Issue 10, p1055
- ISSN
1050-7256
- Publication type
Article
- DOI
10.1089/thy.2008.0101