title: Lack of GNAQ germline mutations in uveal melanoma patients with high risk for hereditary cancer predisposition.
abstract: A high frequency of somatic mutation in GNAQ has been reported in uveal melanoma (UM). GNAQ is located in the chromosomal band 9q21, the same chromosomal band that harbors a putative candidate gene for hereditary UM. We investigated the frequency of germline sequence alterations in the GNAQ gene in UM patients with increased predisposition to hereditary cancer. A total of 44 high risk UM patients were studied including three patients with a family history of UM, 15 patients with a family history of cutaneous melanoma (CM), three patients with early age at onset of their UM (<30 years) and 23 patients with strong family history of cancer and/or personal history of multiple primary tumors. Mutational screening of the seven exons of GNAQ and nearby intronic sequence was carried out by direct sequencing. We identified two deep intronic variants but no potential pathogenic mutations in GNAQ. Our results exclude GNAQ as a candidate gene in UM patients with a high risk for hereditary cancer predisposition.
authors.affiliation: Department of Ophthalmology, The Ohio State University, 400 W 12th Ave, Rm 202, Columbus, OH 43210, USA. Mohamed.abdel-rahman@osumc.edu
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Abdel-Rahman
authors.forename: Robert
authors.initials: R
authors.lastname: Pilarski
authors.forename: James B
authors.initials: JB
authors.lastname: Massengill
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Christopher
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Davidorf
mesh_terms: D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D008545:Melanoma / Q000209:etiology / Q000235:genetics*; D014604:Uveal Neoplasms / Q000209:etiology / Q000235:genetics*; D000098943:Uveal Melanoma
chemical_list: C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D043802:GTP-Binding Protein alpha Subunits, Gq-G11