This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fagin, J. A. Search for Related Content PubMed PubMed Citation Articles by Fagin, J. A.

Minireview: Branded from the Start—Distinct Oncogenic Initiating Events May Determine Tumor Fate in the Thyroid

Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0547

Address all correspondence and requests for reprints to: James A. Fagin, M.D., Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, Vontz Center for Molecular Sciences, 3125 Eden Avenue, Cincinnati, Ohio 45267-0547. E-mail: James.Fagin{at}uc.edu.

Thyroid follicular neoplasms commonly have aneuploidy, presumably due to chromosomal instability. This property is associated with a greater malignant potential and worse prognosis. Recently, there has been considerable progress in our understanding of mechanisms that may account for chromosomal instability in cancer cells. Many tumors with chromosomal instability have abnormalities in the cell cycle checkpoint that monitors the fidelity of mitosis. Mutations of Bub1 or BubR1, genes coding for kinases involved in mitotic spindle assembly checkpoint signaling, are found in a small subset of aneuploid tumors. Other components of protein complexes responsible for attachment of kinetochores to microtubules, or for cohesion between sister chromatids, may also be subject to alterations during tumor progression. Here, we also discuss the evidence that certain oncogenic events, such as Ras mutations, may predispose cells to chromosomal instability by favoring inappropriate posttranslational changes in mitotic checkpoint components through activation of upstream kinases during tumor initiation or progression.

This article has been cited by other articles:

				Y. Arlot-Bonnemains, E. Baldini, B. Martin, J.-G. Delcros, M. Toller, F. Curcio, F. S Ambesi-Impiombato, M. D'Armiento, and S. Ulisse Effects of the Aurora kinase inhibitor VX-680 on anaplastic thyroid cancer-derived cell lines Endocr. Relat. Cancer, June 1, 2008; 15(2): 559 - 568. [Abstract] [Full Text] [PDF]

				M. Eszlinger, K. Krohn, A. Kukulska, B. Jarzab, and R. Paschke Perspectives and Limitations of Microarray-Based Gene Expression Profiling of Thyroid Tumors Endocr. Rev., May 1, 2007; 28(3): 322 - 338. [Abstract] [Full Text] [PDF]

				K. Krause, S. Karger, A. Schierhorn, S. Poncin, M.-C. Many, and D. Fuhrer Proteomic Profiling of Cold Thyroid Nodules Endocrinology, April 1, 2007; 148(4): 1754 - 1763. [Abstract] [Full Text] [PDF]

				V. Vasko, A. V. Espinosa, W. Scouten, H. He, H. Auer, S. Liyanarachchi, A. Larin, V. Savchenko, G. L. Francis, A. de la Chapelle, et al. Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion PNAS, February 20, 2007; 104(8): 2803 - 2808. [Abstract] [Full Text] [PDF]

				A. J. Fikaris, A. E. Lewis, A. Abulaiti, O. M. Tsygankova, and J. L. Meinkoth Ras Triggers Ataxia-telangiectasia-mutated and Rad-3-related Activation and Apoptosis through Sustained Mitogenic Signaling J. Biol. Chem., November 17, 2006; 281(46): 34759 - 34767. [Abstract] [Full Text] [PDF]

				A. Abulaiti, A. J. Fikaris, O. M. Tsygankova, and J. L. Meinkoth Ras Induces Chromosome Instability and Abrogation of the DNA Damage Response Cancer Res., November 1, 2006; 66(21): 10505 - 10512. [Abstract] [Full Text] [PDF]

				J. W. B. de Groot, T. P. Links, J. T. M. Plukker, C. J. M. Lips, and R. M. W. Hofstra RET as a Diagnostic and Therapeutic Target in Sporadic and Hereditary Endocrine Tumors Endocr. Rev., August 1, 2006; 27(5): 535 - 560. [Abstract] [Full Text] [PDF]

				R. Malaguarnera, A. Mandarino, E. Mazzon, V. Vella, P. Gangemi, C. Vancheri, P. Vigneri, A. Aloisi, R. Vigneri, and F. Frasca The p53-homologue p63 may promote thyroid cancer progression Endocr. Relat. Cancer, December 1, 2005; 12(4): 953 - 971. [Abstract] [Full Text] [PDF]

				N. Stathatos, I. Bourdeau, A. V. Espinosa, M. Saji, V. V. Vasko, K. D. Burman, C. A. Stratakis, and M. D. Ringel KiSS-1/G Protein-Coupled Receptor 54 Metastasis Suppressor Pathway Increases Myocyte-Enriched Calcineurin Interacting Protein 1 Expression and Chronically Inhibits Calcineurin Activity J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5432 - 5440. [Abstract] [Full Text] [PDF]

				H. De Nicola, J. Szejnfeld, A. F. Logullo, A. M. B. Wolosker, L. R. M. F. Souza, and V. Chiferi Jr Flow Pattern and Vascular Resistive Index as Predictors of Malignancy Risk in Thyroid Follicular Neoplasms J. Ultrasound Med., July 1, 2005; 24(7): 897 - 904. [Abstract] [Full Text] [PDF]

				L. Lacroix, V. Lazar, S. Michiels, H. Ripoche, P. Dessen, M. Talbot, B. Caillou, J.-P. Levillain, M. Schlumberger, and J.-M. Bidart Follicular Thyroid Tumors with the PAX8-PPAR{gamma}1 Rearrangement Display Characteristic Genetic Alterations Am. J. Pathol., July 1, 2005; 167(1): 223 - 231. [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]

				D Fuhrer, M Eszlinger, S Karger, K Krause, C Engelhardt, D Hasenclever, H Dralle, and R Paschke Evaluation of insulin-like growth factor II, cyclooxygenase-2, ets-1 and thyroid-specific thyroglobulin mRNA expression in benign and malignant thyroid tumours Eur. J. Endocrinol., May 1, 2005; 152(5): 785 - 790. [Abstract] [Full Text] [PDF]

				M. L. Motti, D. Califano, G. Troncone, C. De Marco, I. Migliaccio, E. Palmieri, L. Pezzullo, L. Palombini, A. Fusco, and G. Viglietto Complex Regulation of the Cyclin-Dependent Kinase Inhibitor p27kip1 in Thyroid Cancer Cells by the PI3K/AKT Pathway: Regulation of p27kip1 Expression and Localization Am. J. Pathol., March 1, 2005; 166(3): 737 - 749. [Abstract] [Full Text] [PDF]

				M. Sahin, B. L. Allard, M. Yates, J. G. Powell, X.-L. Wang, I. D. Hay, Y. Zhao, J. R. Goellner, T. J. Sebo, S. K. G. Grebe, et al. PPAR{gamma} Staining as a Surrogate for PAX8/PPAR{gamma} Fusion Oncogene Expression in Follicular Neoplasms: Clinicopathological Correlation and Histopathological Diagnostic Value J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 463 - 468. [Abstract] [Full Text] [PDF]

				K. Kwong, R. A. Vaishnav, Y. Liu, N. Subhedar, A. J. Stromberg, M. L. Getchell, and T. V. Getchell Target ablation-induced regulation of macrophage recruitment into the olfactory epithelium of Mip-1{alpha}-/- mice and restoration of function by exogenous MIP-1{alpha} Physiol Genomics, December 15, 2004; 20(1): 73 - 86. [Abstract] [Full Text] [PDF]

				Y. Kato, H. Ying, M. C. Willingham, and S.-Y. Cheng A Tumor Suppressor Role for Thyroid Hormone {beta} Receptor in a Mouse Model of Thyroid Carcinogenesis Endocrinology, October 1, 2004; 145(10): 4430 - 4438. [Abstract] [Full Text] [PDF]

				M. Braga-Basaria, E. Hardy, R. Gottfried, K. D. Burman, M. Saji, and M. D. Ringel 17-Allylamino-17-Demethoxygeldanamycin Activity against Thyroid Cancer Cell Lines Correlates with Heat Shock Protein 90 Levels J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2982 - 2988. [Abstract] [Full Text] [PDF]

				V Vasko, M Saji, E Hardy, M Kruhlak, A Larin, V Savchenko, M Miyakawa, O Isozaki, H Murakami, T Tsushima, et al. Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer J. Med. Genet., March 1, 2004; 41(3): 161 - 170. [Abstract] [Full Text] [PDF]

				F. Frasca, V. Vella, A. Aloisi, A. Mandarino, E. Mazzon, R. Vigneri, and P. Vigneri p73 Tumor-Suppressor Activity Is Impaired in Human Thyroid Cancer Cancer Res., September 15, 2003; 63(18): 5829 - 5837. [Abstract] [Full Text] [PDF]

				M. T. Collins, N. J. Sarlis, M. J. Merino, J. Monroe, S. E. Crawford, J. A. Krakoff, L. C. Guthrie, S. Bonat, P. G. Robey, and A. Shenker Thyroid Carcinoma in the McCune-Albright Syndrome: Contributory Role of Activating Gs{alpha} Mutations J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4413 - 4417. [Abstract] [Full Text] [PDF]

				H. Ying, H. Suzuki, L. Zhao, M. C. Willingham, P. Meltzer, and S.-Y. Cheng Mutant Thyroid Hormone Receptor {beta} Represses the Expression and Transcriptional Activity of Peroxisome Proliferator-activated Receptor {gamma} during Thyroid Carcinogenesis Cancer Res., September 1, 2003; 63(17): 5274 - 5280. [Abstract] [Full Text] [PDF]

				H. Ying, H. Suzuki, H. Furumoto, R. Walker, P. Meltzer, M. C. Willingham, and S.-Y. Cheng Alterations in genomic profiles during tumor progression in a mouse model of follicular thyroid carcinoma Carcinogenesis, September 1, 2003; 24(9): 1467 - 1479. [Abstract] [Full Text] [PDF]

				K. Boelaert, C. J. McCabe, L. A. Tannahill, N. J. L. Gittoes, R. L. Holder, J. C. Watkinson, A. R. Bradwell, M. C. Sheppard, and J. A. Franklyn Pituitary Tumor Transforming Gene and Fibroblast Growth Factor-2 Expression: Potential Prognostic Indicators in Differentiated Thyroid Cancer J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2341 - 2347. [Abstract] [Full Text] [PDF]

				B. J. Tunquist and J. L. Maller Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs Genes & Dev., March 15, 2003; 17(6): 683 - 710. [Full Text] [PDF]

				K. Farrand, B. Delahunt, X.-l. Wang, B. McIver, I. D. Hay, J. R. Goellner, N. L. Eberhardt, and S. K. G. Grebe High Resolution Loss of Heterozygosity Mapping of 17p13 in Thyroid Cancer: Hurthle Cell Carcinomas Exhibit a Small 411-Kilobase Common Region of Allelic Imbalance, Probably Containing a Novel Tumor Suppressor Gene J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4715 - 4721. [Abstract] [Full Text] [PDF]