title: GNAQ and GNA11 mutations occur in 9.5% of mucosal melanoma and are associated with poor prognosis.
abstract: Mucosal melanoma (MM) is a rare subtype of melanoma in Caucasians with extremely poor prognosis, and therapy strategy has not been clearly established for MM. We aimed to investigate the genetic aberrations possibly applicable in targeted therapy of MM. We examined the somatic mutations of GNAQ and GNA11 (GNAQ/11, encoding the guanine nucleotide-binding alpha subunits) in MM and evaluated their correlation to clinicopathologic features of MM.
  
  
  
  This study collected samples from primary lesions of 284 MM patients. Tissue samples were analysed for mutations in exons 4 and 5 of GNAQ/11 in genomic DNA by polymerase chain reaction amplification and Sanger sequencing. Correlations of GNAQ/11 mutations to clinicopathologic features and prognosis of MM were evaluated.
  
  
  
  The overall mutation frequency of GNAQ/11 in MM was 9.5% (27 in 284), with a frequency of 4.6% and 4.9% for GNAQ and GNA11 mutations, respectively. The mutations in exon 5 of GNAQ/11 occurred exclusively in codon 209. GNAQ(Q209L) was the most prevalent variation (92.3% of missense GNAQ mutations). GNAQ/11 mutations were not significantly associated with age, gender, ulceration, and primary anatomic site. The median overall survival for MM patients with GNAQ mutations (16.0 versus 26.0 months, P = 0.031) or GNA11 mutations (15.0 versus 26.0 months, P = 0.039) were significantly shorter than those for patients with wild-type GNAQ and GNA11, respectively.
  
  
  
  Our study suggests that GNAQ and GNA11 mutations occur frequently in MM and may be a prognostic factor for MM. Our data implicate that GNAQ/11 may be potential targets for targeted therapy of MM.
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Xinan
authors: X
authors: Sheng
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Yan
authors: Y
authors: Kong
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Yiqian
authors: Y
authors: Li
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Qiannan
authors: Q
authors: Zhang
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Lu
authors: L
authors: Si
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Chuanliang
authors: C
authors: Cui
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Zhihong
authors: Z
authors: Chi
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Bixia
authors: B
authors: Tang
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Lili
authors: L
authors: Mao
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Bin
authors: B
authors: Lian
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Xuan
authors: X
authors: Wang
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Xieqiao
authors: X
authors: Yan
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Siming
authors: S
authors: Li
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China.
authors: Jie
authors: J
authors: Dai
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Collaborative Innovation Center for Cancer Medicine, Beijing, China. Electronic address: guoj307@126.com.
authors: Jun
authors: J
authors: Guo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
chemical_list: C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: GNA11; GNAQ; Mucosal melanoma; Mutation; Overall survival; Targeted therapy