| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
REVIEW |
Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, 1830 E. Monument St/Suite 333 Baltimore, MD 21287, USA
(Requests for offprints should be addressed to M Xing; Email: mxing1{at}jhmi.edu)
Genetic alteration is the driving force for thyroid tumorigenesis and progression, based upon which novel approaches to the management of thyroid cancer can be developed. A recent important genetic finding in thyroid cancer is the oncogenic T1799A transversion mutation of BRAF (the gene for the B-type Raf kinase, BRAF). Since the initial report of this mutation in thyroid cancer 2 years ago, rapid advancements have been made. BRAF mutation is the most common genetic alteration in thyroid cancer, occurring in about 45% of sporadic papillary thyroid cancers (PTCs), particularly in the relatively aggressive subtypes, such as the tall-cell PTC. This mutation is mutually exclusive with other common genetic alterations, supporting its independent oncogenic role, as demonstrated by transgenic mouse studies that showed BRAF mutation-initiated development of PTC and its transition to anaplastic thyroid cancer. BRAF mutation is mutually exclusive with RET/PTC rearrangement, and also displays a reciprocal age association with this common genetic alteration in thyroid cancer. The T1799A BRAF mutation occurs exclusively in PTC and PTC-derived anaplastic thyroid cancer and is a specific diagnostic marker for this cancer when identified in cytological and histological specimens. This mutation is associated with a poorer clinicopathological outcome and is a novel independent molecular prognostic marker in the risk evaluation of thyroid cancer. Moreover, preclinical and clinical evaluations of the therapeutic value of novel specific mitogen-activated protein kinase pathway inhibitors in thyroid cancer are anticipated. This newly discovered BRAF mutation may prove to have an important impact on thyroid cancer in the clinic.
This article has been cited by other articles:
|
|
 |
|
  K. Hamatani, H. Eguchi, R. Ito, M. Mukai, K. Takahashi, M. Taga, K. Imai, J. Cologne, M. Soda, K. Arihiro, et al. RET/PTC Rearrangements Preferentially Occurred in Papillary Thyroid Cancer among Atomic Bomb Survivors Exposed to High Radiation Dose Cancer Res., September 1, 2008; 68(17): 7176 - 7182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pallante, A. Federico, M. T. Berlingieri, M. Bianco, A. Ferraro, F. Forzati, A. Iaccarino, M. Russo, G. M. Pierantoni, V. Leone, et al. Loss of the CBX7 Gene Expression Correlates with a Highly Malignant Phenotype in Thyroid Cancer Cancer Res., August 15, 2008; 68(16): 6770 - 6778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. B. Friday, C. Yu, G. K. Dy, P. D. Smith, L. Wang, S. N. Thibodeau, and A. A. Adjei BRAF V600E Disrupts AZD6244-Induced Abrogation of Negative Feedback Pathways between Extracellular Signal-Regulated Kinase and Raf Proteins Cancer Res., August 1, 2008; 68(15): 6145 - 6153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Romei, R. Ciampi, P. Faviana, L. Agate, E. Molinaro, V. Bottici, F. Basolo, P. Miccoli, F. Pacini, A. Pinchera, et al. BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer Endocr. Relat. Cancer, June 1, 2008; 15(2): 511 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Nikiforova, G. C. Tseng, D. Steward, D. Diorio, and Y. E. Nikiforov MicroRNA Expression Profiling of Thyroid Tumors: Biological Significance and Diagnostic Utility J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1600 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, M. Ji, W. Wang, Z. Miao, P. Hou, X. Chen, F. Xu, G. Zhu, X. Sun, Y. Li, et al. Association of the T1799A BRAF mutation with tumor extrathyroidal invasion, higher peripheral platelet counts, and over-expression of platelet-derived growth factor-B in papillary thyroid cancer Endocr. Relat. Cancer, March 1, 2008; 15(1): 183 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F Frasca, C Nucera, G Pellegriti, P Gangemi, M Attard, M Stella, M Loda, V Vella, C Giordano, F Trimarchi, et al. BRAF(V600E) mutation and the biology of papillary thyroid cancer Endocr. Relat. Cancer, March 1, 2008; 15(1): 191 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Abubaker, Z. Jehan, P. Bavi, M. Sultana, S. Al-Harbi, M. Ibrahim, A. Al-Nuaim, M. Ahmed, T. Amin, M. Al-Fehaily, et al. Clinicopathological Analysis of Papillary Thyroid Cancer with PIK3CA Alterations in a Middle Eastern Population J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 611 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Ahn, Y. Henderson, Y. Kang, C. Chattopadhyay, P. Holton, M. Wang, K. Briggs, and G. L. Clayman An Orthotopic Model of Papillary Thyroid Carcinoma in Athymic Nude Mice Arch Otolaryngol Head Neck Surg, February 1, 2008; 134(2): 190 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Salajegheh, E B Petcu, R A Smith, and A K-Y Lam Follicular variant of papillary thyroid carcinoma: a diagnostic challenge for clinicians and pathologists Postgrad. Med. J., February 1, 2008; 84(988): 78 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Friday and A. A. Adjei Advances in Targeting the Ras/Raf/MEK/Erk Mitogen-Activated Protein Kinase Cascade with MEK Inhibitors for Cancer Therapy Clin. Cancer Res., January 15, 2008; 14(2): 342 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Santarpia, A. K. El-Naggar, G. J. Cote, J. N. Myers, and S. I. Sherman Phosphatidylinositol 3-Kinase/Akt and Ras/Raf-Mitogen-Activated Protein Kinase Pathway Mutations in Anaplastic Thyroid Cancer J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 278 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
D. W. Ball, N. Jin, D. M. Rosen, A. Dackiw, D. Sidransky, M. Xing, and B. D. Nelkin Selective Growth Inhibition in BRAF Mutant Thyroid Cancer by the Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor AZD6244 J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4712 - 4718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Liu, Z. Liu, D. Jiang, A. P. Dackiw, and M. Xing Inhibitory Effects of the Mitogen-Activated Protein Kinase Kinase Inhibitor CI-1040 on the Proliferation and Tumor Growth of Thyroid Cancer Cells with BRAF or RAS Mutations J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4686 - 4695. [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]
|
|
|
|
|
|
Y. C. Henderson, M. J. Fredrick, and G. L. Clayman Differential Responses of Human Papillary Thyroid Cancer Cell Lines Carrying the RET/PTC1 Rearrangement or a BRAF Mutation to MEK1/2 Inhibitors Arch Otolaryngol Head Neck Surg, August 1, 2007; 133(8): 810 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ciampi, T. J Giordano, K. Wikenheiser-Brokamp, R. J Koenig, and Y. E Nikiforov HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma Endocr. Relat. Cancer, June 1, 2007; 14(2): 445 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A Ellerhorst, A. Sendi-Naderi, M. K Johnson, C. P Cooke, S. M Dang, and A H. Diwan Human melanoma cells express functional receptors for thyroid-stimulating hormone Endocr. Relat. Cancer, December 1, 2006; 13(4): 1269 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Santoro, R. M. Melillo, and A. Fusco RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture. Eur. J. Endocrinol., November 1, 2006; 155(5): 645 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. S. Jo, S. Li, J. H. Song, K. H. Kwon, J. C. Lee, S. Y. Rha, H. J. Lee, J. Y. Sul, G. R. Kweon, H.-k. Ro, et al. Influence of the BRAF V600E Mutation on Expression of Vascular Endothelial Growth Factor in Papillary Thyroid Cancer J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3667 - 3670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mesa Jr., M. Mirza, N. Mitsutake, M. Sartor, M. Medvedovic, C. Tomlinson, J. A Knauf, G. F. Weber, and J. A. Fagin Conditional Activation of RET/PTC3 and BRAFV600E in Thyroid Cells Is Associated with Gene Expression Profiles that Predict a Preferential Role of BRAF in Extracellular Matrix Remodeling. Cancer Res., July 1, 2006; 66(13): 6521 - 6529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Niedziela Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr. Relat. Cancer, June 1, 2006; 13(2): 427 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L Fugazzola, E Puxeddu, N Avenia, C Romei, V Cirello, A Cavaliere, P Faviana, D Mannavola, S Moretti, S Rossi, et al. Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature. Endocr. Relat. Cancer, June 1, 2006; 13(2): 455 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Di Cristofaro, M Silvy, A Lanteaume, M Marcy, P Carayon, and C De Micco Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes. Endocr. Relat. Cancer, June 1, 2006; 13(2): 485 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chiloeches and R. Marais Is BRAF the Achilles' Heel of Thyroid Cancer? Clin. Cancer Res., March 15, 2006; 12(6): 1661 - 1664. [Full Text] [PDF]
|
|
|
|
|
|
T. Foukakis, A. Y. M. Au, G. Wallin, J. Geli, L. Forsberg, R. Clifton-Bligh, B. G. Robinson, W.-O. Lui, J. Zedenius, and C. Larsson The Ras Effector NORE1A Is Suppressed in Follicular Thyroid Carcinomas with a PAX8-PPAR{gamma} Fusion J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1143 - 1149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Salvatore, V. De Falco, P. Salerno, T. C. Nappi, S. Pepe, G. Troncone, F. Carlomagno, R. M. Melillo, S. M. Wilhelm, and M. Santoro BRAF Is a Therapeutic Target in Aggressive Thyroid Carcinoma Clin. Cancer Res., March 1, 2006; 12(5): 1623 - 1629. [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]
|
|
|
|
|
|
J. M. Vieira, S. C R. Santos, C. Espadinha, I. Correia, T. Vag, C. Casalou, B. M. Cavaco, A. L. Catarino, S. Dias, and V. Leite Expression of vascular endothelial growth factor (VEGF) and its receptors in thyroid carcinomas of follicular origin: a potential autocrine loop Eur. J. Endocrinol., November 1, 2005; 153(5): 701 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Vasko, S. Hu, G. Wu, J. C. Xing, A. Larin, V. Savchenko, B. Trink, and M. Xing High Prevalence and Possible de Novo Formation of BRAF Mutation in Metastasized Papillary Thyroid Cancer in Lymph Nodes J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5265 - 5269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wu, E. Mambo, Z. Guo, S. Hu, X. Huang, S. M. Gollin, B. Trink, P. W. Ladenson, D. Sidransky, and M. Xing Uncommon Mutation, but Common Amplifications, of the PIK3CA Gene in Thyroid Tumors J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4688 - 4693. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
