title: Analysis of GNAQ mutations, proliferation and MAPK pathway activation in uveal melanomas.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Pópulo
authors.forename: João
authors.initials: J
authors.lastname: Vinagre
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Lopes
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: D009363:Neoplasm Proteins; D019950:Mitogen-Activated Protein Kinase 1