High Prevalence of BRAF Mutations in Thyroid Cancer: Genetic Evidence for Constitutive Activation of the RET/PTC-RAS-BRAF Signaling Pathway in Papillary Thyroid Carcinoma1

Title: [CANCER RESEARCH 63, 1454 –1457, April 1, 2003]

High Prevalence of BRAF Mutations in Thyroid Cancer: Genetic Evidence for Constitutive Activation of the RET/PTC-RAS-BRAF Signaling Pathway in Papillary Thyroid Carcinoma1

Author: Edna T. Kimura, Marina N. Nikiforova, Zhaowen Zhu, Jeffrey A. Knauf, Yuri E. Nikiforov, and James A. Fagin2

Reference: [PDF-119K]Jun 2009 [CANCER RESEARCH 63, 1454–1457, April 1, 2003] Advances in Brief

Keywords:

Abstract: Thyroid papillary cancers (PTCs) are associated with activating mutations of genes coding for RET or TRK tyrosine kinase receptors, as well as of RAS genes. Activating mutations of BRAF were reported recently in most melanomas and a small proportion of colorectal tumors. Here we show that a somatic mutation of BRAF, V599E, is the most common genetic change in PTCs (28 of 78; 35.8%). BRAFV599E mutations were unique to PTCs, and not found in any of the other types of differentiated follicular neoplasms arising from the same cell type (0 of 46). Moreover, there was no overlap between PTC with RET/PTC, BRAF, or RAS mutations, which altogether were present in 66% of cases. The lack of concordance for these mutations was highly unlikely to be a chance occurrence. Because these signaling proteins function along the same pathway in thyroid cells, this represents a unique paradigm of human tumorigenesis through mutation of three signaling effectors lying in tandem.

…Ohio 45267 Abstract Thyroid papillary cancers…along the same pathway in thyroid cells, this represents…PTCs3 are the most common thyroid malignant tumor. Character…hallmark of this type of cancer. RET/PTC rearrangements…disasters such as the Chernobyl nuclear reactor accident…

URL: http://path.upmc.edu/people/ynlab/Publication%20PDFs/Nikiforova2003CancerResearch.pdf

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