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International Journal of Molecular Medicine
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Article

TERT promoter hypermethylation is associated with poor prognosis in adrenocortical carcinoma

  • Authors:
    • Fredrika Svahn
    • Johan O. Paulsson
    • Adam Stenman
    • Omid Fotouhi
    • Ninni Mu
    • Timothy D. Murtha
    • Reju Korah
    • Tobias Carling
    • Martin Bäckdahl
    • Na Wang
    • C. Christofer Juhlin
    • Catharina Larsson
  • View Affiliations / Copyright

    Affiliations: Department of Oncology‑Pathology, Karolinska Institutet, Karolinska University Hospital, Cancer Center Karolinska, SE‑17176 Stockholm, Sweden, Department of Surgery, Yale School of Medicine, Yale Endocrine Neoplasia Laboratory, Yale School of Medicine, New Haven, CT 06520, USA, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, SE‑17176 Stockholm, Sweden
  • Pages: 1675-1683
    |
    Published online on: June 20, 2018
       https://doi.org/10.3892/ijmm.2018.3735
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Abstract

Telomere maintenance, most commonly achieved by telomerase activation through induction of the telomerase reverse transcriptase (TERT) gene, is required for cell immortalization, a hallmark of cancer. Adrenocortical carcinoma (ACC) is an endocrine tumor for which TERT promoter mutations and telomerase activation have been reported. The present study assessed alterations of the TERT gene locus and telomere length in relation to clinical characteristics in ACC. In total, 38 cases of ACC with known TERT promoter mutational status were included. TERT promoter methylation densities were assessed by pyrosequencing, and TERT copy numbers and telomere length were determined by quantitative polymerase chain reaction analysis, followed by comparison of the mRNA expression of TERT and clinical parameters. The ACC tissue samples showed increased TERT copy numbers, compared with normal adrenal tissue (NAT) samples (P=0.001). Mutually exclusive TERT copy number gains or promoter mutation were present in 70% of the ACC samples. The ACC tissues exhibited higher levels of CpG promoter methylation of all eight CpG sites investigated within the ‑578 to ‑541 bp (Region A), compared with the NATs (P=0.001). High methylation density at this region was associated with metastatic disease and/or relapse, poor survival rates and higher European Network for the Study of Adrenal Tumor stage (P<0.05). The mRNA expression of TERT was inversely correlated with methylation density at ‑162 to ‑100 bp (Region B). Correlation was observed between relative telomere length and the gene expression of TERT. It was concluded that epigenetic alterations of the TERT promoter are frequent and associated with advanced disease and poorer clinical outcome in ACC.
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Copy and paste a formatted citation
Spandidos Publications style
Svahn F, Paulsson JO, Stenman A, Fotouhi O, Mu N, Murtha TD, Korah R, Carling T, Bäckdahl M, Wang N, Wang N, et al: TERT promoter hypermethylation is associated with poor prognosis in adrenocortical carcinoma. Int J Mol Med 42: 1675-1683, 2018.
APA
Svahn, F., Paulsson, J.O., Stenman, A., Fotouhi, O., Mu, N., Murtha, T.D. ... Larsson, C. (2018). TERT promoter hypermethylation is associated with poor prognosis in adrenocortical carcinoma. International Journal of Molecular Medicine, 42, 1675-1683. https://doi.org/10.3892/ijmm.2018.3735
MLA
Svahn, F., Paulsson, J. O., Stenman, A., Fotouhi, O., Mu, N., Murtha, T. D., Korah, R., Carling, T., Bäckdahl, M., Wang, N., Juhlin, C. C., Larsson, C."TERT promoter hypermethylation is associated with poor prognosis in adrenocortical carcinoma". International Journal of Molecular Medicine 42.3 (2018): 1675-1683.
Chicago
Svahn, F., Paulsson, J. O., Stenman, A., Fotouhi, O., Mu, N., Murtha, T. D., Korah, R., Carling, T., Bäckdahl, M., Wang, N., Juhlin, C. C., Larsson, C."TERT promoter hypermethylation is associated with poor prognosis in adrenocortical carcinoma". International Journal of Molecular Medicine 42, no. 3 (2018): 1675-1683. https://doi.org/10.3892/ijmm.2018.3735
Copy and paste a formatted citation
x
Spandidos Publications style
Svahn F, Paulsson JO, Stenman A, Fotouhi O, Mu N, Murtha TD, Korah R, Carling T, Bäckdahl M, Wang N, Wang N, et al: TERT promoter hypermethylation is associated with poor prognosis in adrenocortical carcinoma. Int J Mol Med 42: 1675-1683, 2018.
APA
Svahn, F., Paulsson, J.O., Stenman, A., Fotouhi, O., Mu, N., Murtha, T.D. ... Larsson, C. (2018). TERT promoter hypermethylation is associated with poor prognosis in adrenocortical carcinoma. International Journal of Molecular Medicine, 42, 1675-1683. https://doi.org/10.3892/ijmm.2018.3735
MLA
Svahn, F., Paulsson, J. O., Stenman, A., Fotouhi, O., Mu, N., Murtha, T. D., Korah, R., Carling, T., Bäckdahl, M., Wang, N., Juhlin, C. C., Larsson, C."TERT promoter hypermethylation is associated with poor prognosis in adrenocortical carcinoma". International Journal of Molecular Medicine 42.3 (2018): 1675-1683.
Chicago
Svahn, F., Paulsson, J. O., Stenman, A., Fotouhi, O., Mu, N., Murtha, T. D., Korah, R., Carling, T., Bäckdahl, M., Wang, N., Juhlin, C. C., Larsson, C."TERT promoter hypermethylation is associated with poor prognosis in adrenocortical carcinoma". International Journal of Molecular Medicine 42, no. 3 (2018): 1675-1683. https://doi.org/10.3892/ijmm.2018.3735
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