BIOMAT Database Logo BIOMAT Database Logo

Differentiating alternative splice variant patterns of human telomerase reverse transcriptase in thyroid neoplasms. 2008

Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.

BACKGROUND Although fine-needle aspiration (FNA) biopsy of thyroid nodules is very sensitive in detecting thyroid malignancy, it remains ambiguous in 20-30% 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 hTERT alternative 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 hTERT patterns. Association of c-myc expression and hTERT patterns was also examined. RESULTS Malignant thyroid tumors exhibited a greater proportion of the active full-length hTERT transcript (0.57 +/- 0.15) than inactive splice variants, alpha(-) (0.13 +/- 0.02), or beta(-)/alpha(-)beta(-) deletion transcripts (0.30 +/- 0.11; p < 0.001). The opposite was observed in benign tumors, which exhibited greater proportions of beta(-)/alpha(-)beta(-) deletion transcripts (0.64 +/- 0.08) than either the full-length (0.19 +/- 0.06) or alpha(-) deletion 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 hTERT isoform. In contrast, c-myc expression, which has been implicated in hTERT regulation, correlated with overall hTERT transcription without specificity for expression of the full-length isoform. CONCLUSIONS These differences in gene expression patterns of hTERT alternative splice variants may provide a useful adjunct to FNA diagnosis of suspicious thyroid tumors.

UI MeSH Term Description Entries
D000236 Adenoma A benign epithelial tumor with a glandular organization. Adenoma, Basal Cell,Adenoma, Follicular,Adenoma, Microcystic,Adenoma, Monomorphic,Adenoma, Papillary,Adenoma, Trabecular,Adenomas,Adenomas, Basal Cell,Adenomas, Follicular,Adenomas, Microcystic,Adenomas, Monomorphic,Adenomas, Papillary,Adenomas, Trabecular,Basal Cell Adenoma,Basal Cell Adenomas,Follicular Adenoma,Follicular Adenomas,Microcystic Adenoma,Microcystic Adenomas,Monomorphic Adenoma,Monomorphic Adenomas,Papillary Adenoma,Papillary Adenomas,Trabecular Adenoma,Trabecular Adenomas
D012372 ROC Curve A graphic means for assessing the ability of a screening test to discriminate between healthy and diseased persons; may also be used in other studies, e.g., distinguishing stimuli responses as to a faint stimuli or nonstimuli. ROC Analysis,Receiver Operating Characteristic,Analysis, ROC,Analyses, ROC,Characteristic, Receiver Operating,Characteristics, Receiver Operating,Curve, ROC,Curves, ROC,ROC Analyses,ROC Curves,Receiver Operating Characteristics
D013964 Thyroid Neoplasms Tumors or cancer of the THYROID GLAND. Cancer of Thyroid,Thyroid Cancer,Cancer of the Thyroid,Neoplasms, Thyroid,Thyroid Adenoma,Thyroid Carcinoma,Adenoma, Thyroid,Adenomas, Thyroid,Cancer, Thyroid,Cancers, Thyroid,Carcinoma, Thyroid,Carcinomas, Thyroid,Neoplasm, Thyroid,Thyroid Adenomas,Thyroid Cancers,Thyroid Carcinomas,Thyroid Neoplasm
D016271 Proto-Oncogene Proteins c-myc Basic helix-loop-helix transcription factors encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis. L-myc Proteins,N-myc Proteins,c-myc Proteins,myc Proto-Oncogene Proteins,p62(c-myc),Proto-Oncogene Products c-myc,Proto-Oncogene Proteins myc,myc Proto-Oncogene Product p62,p62 c-myc,L myc Proteins,N myc Proteins,Proteins myc, Proto-Oncogene,Proto Oncogene Products c myc,Proto Oncogene Proteins c myc,Proto Oncogene Proteins myc,Proto-Oncogene Proteins, myc,c myc Proteins,myc Proto Oncogene Product p62,myc Proto Oncogene Proteins,myc, Proto-Oncogene Proteins,p62 c myc
D017398 Alternative Splicing A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different. RNA Splicing, Alternative,Splicing, Alternative,Alternate Splicing,Nested Transcripts,Alternate Splicings,Alternative RNA Splicing,Alternative RNA Splicings,Alternative Splicings,Nested Transcript,RNA Splicings, Alternative,Splicing, Alternate,Splicing, Alternative RNA,Splicings, Alternate,Splicings, Alternative,Splicings, Alternative RNA,Transcript, Nested,Transcripts, Nested
D018249 Adenoma, Oxyphilic A usually benign glandular tumor composed of oxyphil cells, large cells with small irregular nuclei and dense acidophilic granules due to the presence of abundant MITOCHONDRIA. Oxyphil cells, also known as oncocytes, are found in oncocytomas of the kidney, salivary glands, and endocrine glands. In the thyroid gland, oxyphil cells are known as Hurthle cells and Askanazy cells. Hurthle Cell Tumor,Oncocytoma,Huerthle Cell Tumor,Oxyphilic Adenoma
D018265 Carcinoma, Papillary, Follicular A thyroid neoplasm of mixed papillary and follicular arrangement. Its biological behavior and prognosis is the same as that of a papillary adenocarcinoma of the thyroid. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1271)
D019098 Telomerase An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES. Telomerase Catalytic Subunit,Telomerase Reverse Transcriptase,Telomerase Reverse Transcriptase Catalytic Subunit,Catalytic Subunit, Telomerase,Reverse Transcriptase, Telomerase,Subunit, Telomerase Catalytic,Transcriptase, Telomerase Reverse
D020133 Reverse Transcriptase Polymerase Chain Reaction A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. Polymerase Chain Reaction, Reverse Transcriptase,Reverse Transcriptase PCR,PCR, Reverse Transcriptase,Transcriptase PCR, Reverse

Related Publications

Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
Expression of human telomerase reverse transcriptase (hTERT) in thyroid neoplasms.
January 2018, Journal of B.U.ON. : official journal of the Balkan Union of Oncology,
Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
Human telomerase reverse transcriptase (hTERT) gene expression in thyroid neoplasms.
June 1999, Clinical cancer research : an official journal of the American Association for Cancer Research,
Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
Telomerase activity in thyroid neoplasms evaluated by the expression of human telomerase reverse transcriptase (hTERT).
January 2005, Anticancer research,
Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
Expression of human telomerase reverse transcriptase in thyroid follicular neoplasms: an immunohistochemical study.
January 2005, Endocrine pathology,
Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
Human telomerase reverse transcriptase (hTERT) gene expression in FNA samples from thyroid neoplasms.
December 1999, Surgery,
Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
Human telomerase reverse transcriptase (hTERT) gene expression in FNA samples from thyroid neoplasms.
March 2003, Cancer letters,
Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
The major reverse transcriptase-incompetent splice variant of the human telomerase protein inhibits telomerase activity but protects from apoptosis.
May 2013, Cancer research,
Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
Physiological and pathological significance of human telomerase reverse transcriptase splice variants.
November 2013, Biochimie,
Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
Telomerase reverse transcriptase mutations in thyroid carcinoma.
January 2020, Journal of B.U.ON. : official journal of the Balkan Union of Oncology,
Yongchun Wang, and Jeanne Kowalski, and Hua-Ling Tsai, and Radharani Marik, and Nijaguna Prasad, and Helina Somervell, and Pang-Kuo Lo, and Lauren E Sangenario, and Lars Dyrskjot, and Torben F Orntoft, and William H Westra, and Alan K Meeker, and James R Eshleman, and Christopher B Umbricht, and Martha A Zeiger
Canis familiaris telomerase reverse transcriptase undergoes alternative splicing.
September 2008, Mammalian genome : official journal of the International Mammalian Genome Society,
Copied contents to your clipboard!