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Analysis of GNAQ mutations, proliferation and MAPK pathway activation in uveal melanomas

Authors: Helena, Pópulo; João, Vinagre; José Manuel, Lopes; Paula, Soares;

Analysis of GNAQ mutations, proliferation and MAPK pathway activation in uveal melanomas

Abstract

To study the GNAQ mutational status in a series of uveal melanomas and evaluate possible associations with mitogen-activated protein kinase (MAPK) pathway protein expression and tumour proliferation markers.Mutational analysis was performed by PCR/sequencing of exon 5 of the GNAQ gene in a series of 22 uveal melanomas in which total and phosphorylated extracellular signal-regulated kinase (ERK) 1/2 overexpression without coexistent BRAF and NRAS mutations had previously been observed. Expression of the cell cycle markers (Ki-67, cyclin D1 and p27) was evaluated by immunohistochemistry. The association between GNAQ mutational status, ERK1/2, phospho-ERK1/2, Ki-67, cyclin D1 and p27 expression levels and the clinicopathological prognostic parameters of uveal melanomas was also assessed.GNAQ mutations were found in 36% of uveal melanomas. No associations were found between the GNAQ mutational status and prognostic parameters, the expression of ERK1/2, pERK1/2 and cell cycle markers.The results of this study suggest that GNAQ mutated uveal melanomas do not exhibit a higher deregulation of proliferation or higher activation of the MAPK signalling pathway than uveal melanomas without GNAQ overactivation.

Keywords

Male, Mitogen-Activated Protein Kinase 1, Uveal Neoplasms, Cell Cycle, DNA Mutational Analysis, Exons, Middle Aged, Prognosis, Immunohistochemistry, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Uveal Melanoma, Mutation, Tumor Cells, Cultured, Humans, Female, Melanoma, Signal Transduction

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
37
Top 10%
Top 10%
Top 10%