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Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing.

Publication ,  Journal Article
Xing, M; Usadel, H; Cohen, Y; Tokumaru, Y; Guo, Z; Westra, WB; Tong, BC; Tallini, G; Udelsman, R; Califano, JA; Ladenson, PW; Sidransky, D
Published in: Cancer Res
May 1, 2003

Thyroid-stimulating hormone receptor (TSHR) expression is frequently silenced in epithelial thyroid cancers associated with decreased or absent TSH-promoted iodine uptake. To study the underlying molecular mechanism of decreased TSHR expression, we examined the methylation status of the TSHR gene promoter by sequencing bisulfite-treated DNA from thyroid tumors. After identification of methylated sites by sequencing bisulfite-treated DNA, we used methylation-specific polymerase chain reaction and found frequent CpG methylation in papillary thyroid cancer (23 of 39 patients; 59%) and follicular thyroid cancers (7 of 15 patients; 47%). In contrast, we saw no methylation in normal thyroid tissues and benign adenomas (0 of 8 patients; 0%). In human thyroid tumor cell lines, we observed that TSHR was normally expressed at the protein and mRNA level in cells where the TSHR gene was unmethylated, whereas it was silenced in cell lines where the TSHR promoter was hypermethylated. Treatment of the latter cells with a demethylating agent partially restored TSHR expression. We thus demonstrate aberrant methylation of human TSHR as a likely molecular pathway responsible for the silencing of this gene in thyroid cancers. We propose that methylation of TSHR may provide a novel diagnostic marker of malignancy and a basis for potential use of demethylating agents in conjunction with TSH-promoted radioiodine therapy for epithelial thyroid cancers.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

May 1, 2003

Volume

63

Issue

9

Start / End Page

2316 / 2321

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Thyroid Neoplasms
  • Receptors, Thyrotropin
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Genetic Markers
  • Gene Silencing
  • Epithelial Cells
  • DNA Methylation
  • Adenoma
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xing, M., Usadel, H., Cohen, Y., Tokumaru, Y., Guo, Z., Westra, W. B., … Sidransky, D. (2003). Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing. Cancer Res, 63(9), 2316–2321.
Xing, Mingzhao, Henning Usadel, Yoram Cohen, Yutaka Tokumaru, Zhongmin Guo, William B. Westra, Betty C. Tong, et al. “Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing.Cancer Res 63, no. 9 (May 1, 2003): 2316–21.
Xing M, Usadel H, Cohen Y, Tokumaru Y, Guo Z, Westra WB, et al. Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing. Cancer Res. 2003 May 1;63(9):2316–21.
Xing M, Usadel H, Cohen Y, Tokumaru Y, Guo Z, Westra WB, Tong BC, Tallini G, Udelsman R, Califano JA, Ladenson PW, Sidransky D. Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing. Cancer Res. 2003 May 1;63(9):2316–2321.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

May 1, 2003

Volume

63

Issue

9

Start / End Page

2316 / 2321

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Thyroid Neoplasms
  • Receptors, Thyrotropin
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Genetic Markers
  • Gene Silencing
  • Epithelial Cells
  • DNA Methylation
  • Adenoma