title: Mutation frequencies of GNAQ, GNA11, BAP1, SF3B1, EIF1AX and TERT in uveal melanoma: detection of an activating mutation in the TERT gene promoter in a single case of uveal melanoma.
abstract: BACKGROUND
  Uveal melanoma is the most frequent primary tumour of the eye. It is molecularly clearly distinct from cutaneous melanoma and shows a different pattern of driver mutations. The influence of sunlight ultraviolet (UV) exposure on the aetiology of uveal melanoma is a matter of debate. The recent identification of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene with UV-induced cytidine-to-thymidine transitions in cutaneous melanoma prompted us to investigate whether these mutations also occur in uveal melanoma.
  
  
  METHODS
  We analysed 50 cases of uveal melanoma obtained from enucleation surgery for mutations in the genes GNAQ, GNA11, BAP1, SF3B1, EIFAX1 and TERT, measured gene expression using microarrays and analysed gene copy numbers by SNP arrays.
  
  
  RESULTS
  We detected a TERT mutation in only one case of a 57-year-old white male patient with clinical and histopathological features typical for uveal melanoma. The tumour showed mutations in GNA11 and EIF1AX that are typical for uveal melanoma and absent from cutaneous melanoma. No mutations were detected in GNAQ, BAP1 and SF3B1 that are frequently mutated in uveal melanoma. Both copies of chromosome 3 were retained. Several tumours among which the one carrying the TERT promoter mutation showed elevated TERT expression. Consistent with previous reports, GNAQ is inversely associated with chromosome 3 monosomy and metastasis. BAP1 mutations are significantly associated with chromosome 3 monosomy but not with relapse.
  
  
  CONCLUSIONS
  These data indicate that TERT mutations are rare in uveal melanoma. No conclusion can be drawn on their potential influence on tumour progression.
authors.affiliation: Molecular Diagnostics, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Dono
authors.affiliation: Integrated Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Angelini
authors.affiliation: Laboratory of Genetics, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cecconi
authors.affiliation: Integrated Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Amaro
authors.affiliation: Integrated Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: A I
authors.initials: AI
authors.lastname: Esposito
authors.affiliation: Integrated Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Mirisola
authors.affiliation: Laboratory of Genetics, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Maric
authors.affiliation: Ocular Oncology Center, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Lanza
authors.affiliation: Ocular Oncology Center, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Nasciuti
authors.affiliation: 1] Laboratory of Genetics, E.O. Ospedali Galliera, Genova, Italy [2] DISTAV, University of Genova, Genova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Viaggi
authors.affiliation: Anatomy and Histopathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gualco
authors.affiliation: Anatomy and Histopathology, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bandelloni
authors.affiliation: Anatomy and Histopathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Truini
authors.affiliation: Integrated Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: D A
authors.initials: DA
authors.lastname: Coviello
authors.affiliation: Molecular Diagnostics, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Zupo
authors.affiliation: Integrated Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Mosci
authors.affiliation: Integrated Molecular Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Pfeffer
mesh_terms: D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D015977:Eukaryotic Initiation Factor-1 / Q000235:genetics; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008666:Metalloendopeptidases / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D017422:Sequence Analysis, DNA; D019098:Telomerase / Q000235:genetics*; D014604:Uveal Neoplasms / Q000235:genetics*; D000098943:Uveal Melanoma
chemical_list: D015977:Eukaryotic Initiation Factor-1; C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; C026022:eukaryotic peptide initiation factor-1A; C509186:TERT protein, human; D019098:Telomerase; C104933:BaP1 metalloproteinase; D008666:Metalloendopeptidases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11