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Telomerase-Dependent and Independent Telomere Maintenance and its Clinical Implications in Medullary Thyroid Carcinoma
- Source :
- The Journal of Clinical Endocrinology and Metabolism
- Publication Year :
- 2014
- Publisher :
- The Endocrine Society, 2014.
-
Abstract
- Context: Telomere maintenance via telomerase activation and the alternative lengthening of telomeres (ALT) mechanism was assessed in medullary thyroid carcinoma. Setting and Design: In total, 42 medullary thyroid carcinomas (MTC) were studied including 24 rearranged during transfection (RET)- mutated cases. Relative telomerase reverse transcriptase (TERT) expression, splice forms, and telomere length were determined by PCR-based methods, and telomerase activity by ELISA. The ALT mechanism was detected by Southern blot analysis and immunofluorescence. Results: TERT expression and telomerase activity were detected in 21/42 tumors (50%), and was independent of the common somatic M918T RET mutation. Mean telomere length was shorter in MTCs compared with thyroids. Telomerase activation was associated with large tumor size (P = .027), advanced clinical stage (P = .0001), and short survival (P = .0001). Full-length TERT and the α− and β−-deletion forms were revealed, and the full-length form was associated with short survival (P = .04). A subset of cases without telomerase activation showed involvement of the ALT mechanism, which was associated with a low MIB-1 proliferation index (P = .024). Conclusions: Stabilization of telomeres by telomerase activation occurs in half of the MTCs and by the ALT mechanism in a subset of cases. Telomerase activation may be used as an additional prognostic marker in medullary thyroid carcinoma.
- Subjects :
- Adult
Male
medicine.medical_specialty
Telomerase
Adolescent
Endocrinology, Diabetes and Metabolism
DNA Mutational Analysis
Clinical Biochemistry
Context (language use)
Biology
Biochemistry
Thyroid carcinoma
Young Adult
Endocrinology
Telomere Homeostasis
Internal medicine
medicine
Humans
Telomerase reverse transcriptase
Thyroid Neoplasms
Aged
Southern blot
Aged, 80 and over
JCEM Online: Advances in Genetics
Proto-Oncogene Proteins c-ret
Biochemistry (medical)
Middle Aged
Telomere
Prognosis
Survival Analysis
Molecular biology
Carcinoma, Neuroendocrine
HEK293 Cells
Telomere maintenance via telomerase
Female
HeLa Cells
Subjects
Details
- ISSN :
- 19457197 and 0021972X
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- The Journal of Clinical Endocrinology & Metabolism
- Accession number :
- edsair.doi.dedup.....e1d13440792d9691f8ac37abf30a7f7a