Mutations in BRAF are rare in the follicular variant of papillary thyroid carcinoma (FV-PTC). OBJECTIVE: We identified and functionally characterized a novel T599I-VKSR(600-603)del BRAF mutation in a FV-PTC patient. We analyzed in vitro the effects of this novel mutation in comparison with other thyroid cancer-associated mutations. DESIGN: Expression vectors for the BRAF mutants were generated and their in vitro kinase activity, signaling along the MAPK pathway, and capability of stimulating transcription from an AP1-responsive reporter evaluated. RESULTS: BRAF kinase and signaling were increased to a similar extent by the T599I-VKSR (600-603)del, V600E, and K601E mutations. Instead, the G474R, a mutation previously found in a FV-PTC, knocked down the BRAF kinase and its intracellular signaling. Some cancer-associated low-activity BRAF mutants stimulate the MAPK cascade via CRAF; however, the G474R protein lacked also this property. CONCLUSION: The T599I-VKSR(600-603)del is a novel gain-of-function mutation that targets BRAF in FV-PTC. Moreover, G474R is the first example of a mutation knocking down enzymatic BRAF activity in a FV-PTC. These findings underscore the importance of functional studies to characterize the role of BRAF mutations associated with thyroid cancer.

Functional Characterization of the Novel T599I-VKSRdel BRAF Mutation in a Follicular Variant Papillary Thyroid Carcinoma / DE FALCO, V.; Giannini, R.; Tamburrino, Anna; Ugolini, C.; Lupi, C.; Puxeddu, E.; Santoro, Massimo; Basolo, F.. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - STAMPA. - 93:11(2008), pp. 4398-4402. [10.1210/jc.2008-0887]

Functional Characterization of the Novel T599I-VKSRdel BRAF Mutation in a Follicular Variant Papillary Thyroid Carcinoma

TAMBURRINO, ANNA;SANTORO, MASSIMO;
2008

Abstract

Mutations in BRAF are rare in the follicular variant of papillary thyroid carcinoma (FV-PTC). OBJECTIVE: We identified and functionally characterized a novel T599I-VKSR(600-603)del BRAF mutation in a FV-PTC patient. We analyzed in vitro the effects of this novel mutation in comparison with other thyroid cancer-associated mutations. DESIGN: Expression vectors for the BRAF mutants were generated and their in vitro kinase activity, signaling along the MAPK pathway, and capability of stimulating transcription from an AP1-responsive reporter evaluated. RESULTS: BRAF kinase and signaling were increased to a similar extent by the T599I-VKSR (600-603)del, V600E, and K601E mutations. Instead, the G474R, a mutation previously found in a FV-PTC, knocked down the BRAF kinase and its intracellular signaling. Some cancer-associated low-activity BRAF mutants stimulate the MAPK cascade via CRAF; however, the G474R protein lacked also this property. CONCLUSION: The T599I-VKSR(600-603)del is a novel gain-of-function mutation that targets BRAF in FV-PTC. Moreover, G474R is the first example of a mutation knocking down enzymatic BRAF activity in a FV-PTC. These findings underscore the importance of functional studies to characterize the role of BRAF mutations associated with thyroid cancer.
2008
Functional Characterization of the Novel T599I-VKSRdel BRAF Mutation in a Follicular Variant Papillary Thyroid Carcinoma / DE FALCO, V.; Giannini, R.; Tamburrino, Anna; Ugolini, C.; Lupi, C.; Puxeddu, E.; Santoro, Massimo; Basolo, F.. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - STAMPA. - 93:11(2008), pp. 4398-4402. [10.1210/jc.2008-0887]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/346942
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