| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
Division of Endocrinology and Metabolism [M. X., P. W. L.], Department of Otolaryngology-Head and Neck Surgery [H. U., Y. C., Y. T., Z. G., B. C. T., J. A. C., D. S.], and Department of Pathology [W. B. W.], the Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Departments of Pathology and Surgery, Yale University School of Medicine, New Haven, Connecticut 06520 [G. T., R. U.]
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.
This article has been cited by other articles:
|
|
 |
|
  G. Riesco-Eizaguirre and P. Santisteban New insights in thyroid follicular cell biology and its impact in thyroid cancer therapy Endocr. Relat. Cancer, December 1, 2007; 14(4): 957 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Xing BRAF Mutation in Papillary Thyroid Cancer: Pathogenic Role, Molecular Bases, and Clinical Implications Endocr. Rev., December 1, 2007; 28(7): 742 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Joseph, M. Ji, D. Liu, P. Hou, and M. Xing Lack of Mutations in the Thyroid Hormone Receptor (TR) {alpha} and Genes but Frequent Hypermethylation of the TR Gene in Differentiated Thyroid Tumors J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4766 - 4770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R Rowe, B. G Bentz, and J. S Bentz Detection of BRAF V600E activating mutation in papillary thyroid carcinoma using PCR with allele-specific fluorescent probe melting curve analysis J. Clin. Pathol., November 1, 2007; 60(11): 1211 - 1215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Smith, C.-Y. Fan, C. Zou, D. Bodenner, and M. S. Kokoska Methylation Status of Genes in Papillary Thyroid Carcinoma Arch Otolaryngol Head Neck Surg, October 1, 2007; 133(10): 1006 - 1011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C.G. van Staveren, D. W. Solis, L. Delys, L. Duprez, G. Andry, B. Franc, G. Thomas, F. Libert, J. E. Dumont, V. Detours, et al. Human Thyroid Tumor Cell Lines Derived from Different Tumor Types Present a Common Dedifferentiated Phenotype Cancer Res., September 1, 2007; 67(17): 8113 - 8120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Xing Gene Methylation in Thyroid Tumorigenesis Endocrinology, March 1, 2007; 148(3): 948 - 953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, S. Hu, P. Hou, D. Jiang, S. Condouris, and M. Xing Suppression of BRAF/MEK/MAP Kinase Pathway Restores Expression of Iodide-Metabolizing Genes in Thyroid Cells Expressing the V600E BRAF Mutant Clin. Cancer Res., February 15, 2007; 13(4): 1341 - 1349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hu, M. Ewertz, R. P. Tufano, M. Brait, A. L. Carvalho, D. Liu, A. P. Tufaro, S. Basaria, D. S. Cooper, D. Sidransky, et al. Detection of Serum Deoxyribonucleic Acid Methylation Markers: A Novel Diagnostic Tool for Thyroid Cancer J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 98 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xing, W. H. Westra, R. P. Tufano, Y. Cohen, E. Rosenbaum, K. J. Rhoden, K. A. Carson, V. Vasko, A. Larin, G. Tallini, et al. BRAF Mutation Predicts a Poorer Clinical Prognosis for Papillary Thyroid Cancer J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6373 - 6379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Hoque, E. Rosenbaum, W. H. Westra, M. Xing, P. Ladenson, M. A. Zeiger, D. Sidransky, and C. B. Umbricht Quantitative Assessment of Promoter Methylation Profiles in Thyroid Neoplasms J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4011 - 4018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Xing BRAF mutation in thyroid cancer Endocr. Relat. Cancer, June 1, 2005; 12(2): 245 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kesmodel, I. Prabakaran, R. Canter, C. Menon, K. Molnar-Kimber, and D. Fraker Virus-Mediated Oncolysis of Thyroid Cancer by a Replication-Selective Adenovirus Driven by a Thyroglobulin Promoter-Enhancer Region J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3440 - 3448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xing, R. P. Tufano, A. P. Tufaro, S. Basaria, M. Ewertz, E. Rosenbaum, P. J. Byrne, J. Wang, D. Sidransky, and P. W. Ladenson Detection of BRAF Mutation on Fine Needle Aspiration Biopsy Specimens: A New Diagnostic Tool for Papillary Thyroid Cancer J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2867 - 2872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-T. Zhang, X.-F. Chen, M.-H. Wang, J.-C. Wang, Q.-Y. Qi, R.-M. Zhang, W.-Q. Xu, Q.-Y. Fei, F. Wang, Q.-Q. Cheng, et al. Defective Expression of Transforming Growth Factor {beta} Receptor Type II Is Associated with CpG Methylated Promoter in Primary Non-Small Cell Lung Cancer Clin. Cancer Res., April 1, 2004; 10(7): 2359 - 2367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xing, V. Vasko, G. Tallini, A. Larin, G. Wu, R. Udelsman, M. D. Ringel, P. W. Ladenson, and D. Sidransky BRAF T1796A Transversion Mutation in Various Thyroid Neoplasms J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1365 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xing, Y. Cohen, E. Mambo, G. Tallini, R. Udelsman, P. W. Ladenson, and D. Sidransky Early Occurrence of RASSF1A Hypermethylation and Its Mutual Exclusion with BRAF Mutation in Thyroid Tumorigenesis Cancer Res., March 1, 2004; 64(5): 1664 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xing, Y. Tokumaru, G. Wu, W. B. Westra, P. W. Ladenson, and D. Sidransky Hypermethylation of the Pendred Syndrome Gene SLC26A4 Is an Early Event in Thyroid Tumorigenesis Cancer Res., May 1, 2003; 63(9): 2312 - 2315. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
