GNAQ and GNA11 mutations occur in 9.5% of mucosal melanoma and are associated with poor prognosis.
GNAQ and GNA11 mutations occur in 9.5% of mucosal melanoma and are associated with poor prognosis.
复制标题
GNAQ%20和%20GNA11%20突变%20发生%20在%209.5%%20的%20粘膜%20黑色素瘤%20和%20%20与%20不良%20预后相关。
DOI：
10.1016/j.ejca.2016.06.019
复制
发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Jun Guo
中科院分区：
文献类型：
--
作者：
Xieqiao Yan;Siming Li;Jie Dai;Jun Guo
粘膜黑色素瘤是一种罕见的高加索黑色素瘤亚型，预后极差，治疗策略尚不明确。本研究旨在研究GNAQ和GNA11基因突变在MM靶向治疗中的应用。我们检测了MM中GNAQ和GNA11的体细胞突变，并评价其与MM临床病理特征的相关性。组织标本用聚合酶链式反应扩增和Sanger测序分析GNAQ/11in基因组DNA外显子4和5的突变。结果284例MM中GNAQ/11基因突变27例，占9.5%，其中GNAQ/11基因突变占4.6%，GNA11基因突变占4.9%。GNAQ/11基因第5外显子突变仅发生在209密码子。GNAQ209L是最常见的变异(92.3%的错义GNAQ突变)，GNAQ/11突变与年龄、性别、溃疡和原发解剖部位无关。携带GNAQ突变和GNA11突变的MM患者的中位总生存期分别为16.0月和26.0月(P=0.031)和26.0月和26.0月(P=0.039)。结论GNAQ和GNA11突变在MM中发生频率较高，可能是MM的预后因素。
BackgroundMucosal 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 ofGNAQandGNA11(GNAQ/11, encoding the guanine nucleotide-binding alpha subunits) in MM and evaluated their correlation to clinicopathologic features of MM.MethodsThis study collected samples from primary lesions of 284 MM patients. Tissue samples were analysed for mutations in exons 4 and 5 ofGNAQ/11in genomic DNA by polymerase chain reaction amplification and Sanger sequencing. Correlations ofGNAQ/11mutations to clinicopathologic features and prognosis of MM were evaluated.ResultsThe overall mutation frequency ofGNAQ/11in MM was 9.5% (27 in 284), with a frequency of 4.6% and 4.9% forGNAQandGNA11mutations, respectively. The mutations in exon 5 ofGNAQ/11occurred exclusively in codon 209. GNAQQ209Lwas the most prevalent variation (92.3% of missenseGNAQmutations).GNAQ/11mutations were not significantly associated with age, gender, ulceration, and primary anatomic site. The median overall survival for MM patients withGNAQmutations (16.0 versus 26.0 months,P= 0.031) orGNA11mutations (15.0 versus 26.0 months,P= 0.039) were significantly shorter than those for patients with wild-typeGNAQandGNA11, respectively.ConclusionsOur study suggests thatGNAQandGNA11mutations 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.
登录
查看更多内容
影响因子：
5.7
作者：
Wu X;Li J;Zhu M;Fletcher JA;Hodi FS
通讯作者：
Hodi FS
影响因子：
10.3
作者：
A. Tsianakas;Markus Böhm;V. Getova;D. Metze;N. Eter;T. Spieker;A. Bräuninger;T. Luger;M. Schiller;C. Sunderkötter
通讯作者：
A. Tsianakas;Markus Böhm;V. Getova;D. Metze;N. Eter;T. Spieker;A. Bräuninger;T. Luger;M. Schiller;C. Sunderkötter
影响因子：
3.8
作者：
Kim CY;Kim DW;Kim K;Curry J;Torres-Cabala C;Patel S
通讯作者：
Patel S
DOI：
10.1126/science.1194472
发表时间：
2010-12-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Harbour JW;Onken MD;Roberson ED;Duan S;Cao L;Worley LA;Council ML;Matatall KA;Helms C;Bowcock AM
通讯作者：
Bowcock AM
影响因子：
30.8
作者：
Wiesner, Thomas;Obenauf, Anna C.;Murali, Rajmohan;Fried, Isabella;Griewank, Klaus G.;Ulz, Peter;Windpassinger, Christian;Wackernagel, Werner;Loy, Shea;Wolf, Ingrid;Viale, Agnes;Lash, Alex E.;Pirun, Mono;Socci, Nicholas D.;Ruetten, Arno;Palmedo, Gabriele;Abramson, David;Offit, Kenneth;Ott, Arthur;Becker, Juergen C.;Cerroni, Lorenzo;Kutzner, Heinz;Bastian, Boris C.;Speicher, Michael R.
通讯作者：
Speicher, Michael R.