A novel complex BRAF mutation detected in a solid variant of papillary thyroid carcinoma.
ABSTRACT BRAF gene mutations are identified in about 45% of papillary thyroid carcinomas (PTC) and represent the most common genetic event in this tumor. Here, we report a case of PTC, solid variant, with a complex BRAF mutation that involves one nucleotide substitution, C1796T, and a CTT triplet insertion, 1798_1799insCTT, located on the same allele. This mutation leads to the replacement of a threonine with an isoleucine, T599I, and replacement of a valine with an alanine and a leucine, V600delinsAL. This mutation was identified both in the preoperative fine needle aspirate sample and in the surgical specimen after total thyroidectomy. Other rare BRAF mutations in PTC are reviewed.
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ABSTRACT: The accuracy of cancer detection in thyroid nodules by fine-needle aspiration (FNA) cytology and prognostication of thyroid cancer needs further improvement and can benefit from testing for molecular alterations known to occur in thyroid tumors. Recent studies have demonstrated the feasibility of mutation detection in clinical FNA samples from thyroid nodules and their contribution to improving the diagnostic accuracy of FNA cytology. It appears that molecular testing is most beneficial for thyroid FNA samples with indeterminate cytology, where it can resolve the diagnosis in a significant number of cases. In addition to BRAF mutation, which has been studied most extensively, detection of RAS, RET/PTC, and PAX8/PPARgamma mutations also contribute substantially to cancer diagnosis. Some of these molecular markers, particularly BRAF, can also be used for tumor prognostication. In clinical setting, molecular testing of thyroid FNA samples and surgically removed tumors should utilize a restricted number of techniques that provide high accuracy and specificity of mutation detection. Testing for cancer-specific mutations in thyroid FNA samples and surgically removed tumor tissues increases diagnostic accuracy of FNA cytology and offers better prognostication of thyroid cancer.Thyroid: official journal of the American Thyroid Association 11/2009; 19(12):1351-61. · 2.60 Impact Factor
Article: Clinical impact of the detection of BRAF mutations in thyroid pathology: potential usefulness as diagnostic, prognostic and theragnostic applications.[show abstract] [hide abstract]
ABSTRACT: A BRAF somatic mutation at residue 600 of the BRAF protein (BRAFV600E) is highly prevalent in papillary thyroid carcinomas (PTC). This mutation occurs in approximately 44% (from 29% to 83%) of PTC depending on the different studies. BRAFV600E is almost always found in PTC with a papillary or a mixed follicular/papillary architecture, being rarer in other subtypes of PTC. The discovery of the BRAFV600E mutation in tissue and fine-needle aspiration (FNA) is diagnostic for PTC and has been frequently associated with worse clinical prognosis. However, some studies failed to reveal this prognostic association. Transcriptional and post-transcriptional modulation of PTC with a BRAF mutation has been evaluated in some recent studies. Current therapeutic approaches targeting BRAF are being tested in clinical trials, particularly in more aggressive PTC. In this review, we will first discuss the diagnostic value of a BRAF mutation for PTC diagnosis. The prognostic role of a BRAFV600E mutation is then outlined and discussed in the context of other well-accepted clinicopathological prognostic parameters for PTC (age, gender, pTNM stage, histological subtype). Finally, the currently and potentially used treatments targeting BRAF in patients with PTC are presented.Current Medicinal Chemistry 03/2010; 17(17):1839-50. · 4.86 Impact Factor