OBJECTIVE: BRAF is an oncogene that is commonly mutated in both melanomas and papillary thyroid carcinomas, usually at position V600E that leads to constitutive activity in the Ras-mitogen-activated protein kinase (MAPK) pathway. We speculated that this same gene may be either mutated at this site, or overexpressed, in pituitary adenomas. DESIGN AND MEASUREMENTS: We sequenced 37 pituitary adenomas for a mutation at the V600E position. In addition, we investigated B-Raf mRNA expression in normal pituitary (n = 5) and nonfunctioning pituitary adenomas (NFPA) (n = 6) by semiquantitative PCR, and in a further 27 pituitary adenomas of various types and 10 normal pituitaries using real-time quantitative PCR. Finally, we explored B-Raf protein expression in 10 normal pituitaries and 12 NFPAs. RESULTS: No sequence mutations for the substitution V600E were identified. B-Raf mRNA was overexpressed in pituitary adenomas compared to normal pituitary, and this was entirely due to overexpression in NFPAs. NFPAs also showed very variable expression of B-Raf protein, but those tumours showing highest levels of B-Raf mRNA expressed the most B-Raf protein. CONCLUSIONS: Mutations previously seen in the majority of melanomas and a substantial minority of papillary thyroid carcinomas are not a frequent finding in pituitary adenomas. However, overexpression of B-Raf mRNA and protein may be a feature of NFPAs, highlighting overactivity of the Ras-B-Raf-MAP kinase pathway in these tumours
A mutation and expression analysis of the oncogene BRAF in pituitary adenomas / I. Ewing, S. Pedder-Smith, G. Franchi, M. Ruscica, M. Emery, V. Vax, E. Garcia, S. Czirják, Z. Hanzély, B. Kola, M. Korbonits, A.B. Grossman. - In: CLINICAL ENDOCRINOLOGY. - ISSN 0300-0664. - 66:3(2007 Mar), pp. 348-352.
|Titolo:||A mutation and expression analysis of the oncogene BRAF in pituitary adenomas|
|Data di pubblicazione:||mar-2007|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1365-2265.2006.02735.x|
|Appare nelle tipologie:||01 - Articolo su periodico|