title: Activating PIK3CA mutations coexist with BRAF or NRAS mutations in a limited fraction of melanomas.
abstract: BACKGROUND
  Activated PI3K-AKT pathway may contribute to decrease sensitivity to inhibitors of key pathogenetic effectors (mutated BRAF, active NRAS or MEK) in melanoma. Functional alterations are deeply involved in PI3K-AKT activation, with a minimal role reported for mutations in PIK3CA, the catalytic subunit of the PI3K gene. We here assessed the prevalence of the coexistence of BRAF/NRAS and PIK3CA mutations in a series of melanoma samples.
  
  
  METHODS
  A total of 245 tumor specimens (212 primary melanomas and 33 melanoma cell lines) was screened for mutations in BRAF, NRAS, and PIK3CA genes by automated direct sequencing.
  
  
  RESULTS
  Overall, 110 (44.9%) samples carried mutations in BRAF, 26 (10.6%) in NRAS, and 24 (9.8%) in PIK3CA. All identified PIK3CA mutations have been reported to induce PI3K activation; those detected in cultured melanomas were investigated for their interference with the antiproliferative activity of the BRAF-mutant inhibitor vemurafenib. A reduced suppression in cell growth was observed in treated cells carrying both BRAF and PIK3CA mutations as compared with those presenting a mutated BRAF only. Among the analysed melanomas, 12/245 (4.9%) samples presented the coexistence of PIK3CA and BRAF/NRAS mutations.
  
  
  CONCLUSIONS
  Our study further suggests that PIK3CA mutations account for a small fraction of PI3K pathway activation and have a limited impact in interfering with the BRAF/NRAS-driven growth in melanoma.
authors: Antonella
authors: A
authors: Manca
authors: Amelia
authors: A
authors: Lissia
authors: Mariaelena
authors: M
authors: Capone
authors: Paolo A
authors: PA
authors: Ascierto
authors: Gerardo
authors: G
authors: Botti
authors: Corrado
authors: C
authors: Caracò
authors: Ignazio
authors: I
authors: Stanganelli
authors: Maria
authors: M
authors: Colombino
authors: MariaCristina
authors: M
authors: Sini
authors: Antonio
authors: A
authors: Cossu
authors: Institute of Biomolecular Chemistry, National Research Council (CNR), Traversa La Crucca 3 - Baldinca Li Punti, Sassari, 07100, Italy. gpalmieri@yahoo.com.
authors: Giuseppe
authors: G
authors: Palmieri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
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