Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma.
Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma.
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DOI：
10.3390/cancers13225749
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发表时间：
2021-11-17
期刊：
影响因子：
5.2
通讯作者：
Sato T
中科院分区：
文献类型：
--
作者：
Terai M;Shimada A;Chervoneva I;Hulse L;Danielson M;Swensen J;Orloff M;Wedegaertner PB;Benovic JL;Aplin AE;Sato T
葡萄膜黑色素瘤是成人最常见的原发性眼内恶性肿瘤。超过90%的UMs在g蛋白中含有互斥的激活突变。这些突变是UM发展的早期事件，被认为是致癌的驱动突变。即使在原发性葡萄膜黑色素瘤治疗后，高达50%的患者随后出现复发，主要是在肝脏。GNAQ突变未被报道与生存相关，而GNA11突变在转移性UM中更为常见。我们研究了GNA11和GNAQ突变的转移性葡萄膜黑色素瘤（MUM）患者转移后生存（Met-to-Death）的相关性。我们发现，GNA11和GNAQ中Q209P与Q209L突变模式的MUM可能预测MUM患者的生存。葡萄膜黑色素瘤是成人最常见的原发性眼部恶性肿瘤，其特征是G蛋白亚基α q （GNAQ）和G蛋白亚基α 11 （GNA11）基因突变。虽然它们被认为是驱动突变，但它们在MUM中的作用仍然难以捉摸。我们研究了MUM的关键体细胞突变及其对患者发生全身转移（Met-to-Death）后生存的影响。通过下一代测序（NGS）分析87例MUM患者的转移灶。GNA11（41/87）和GNAQ（39/87）突变在MUM中最为明显。GNA11突变主要为Q209L(36/41)，而GNAQ突变主要为Q209L（14/39）和Q209P（21/39）。发现表观遗传途径突变BAP1（42/66）、SF3B1（11/66）、FBXW7（2/87）、PBRM1（1/66）、SETD2（1/66）。没有标本有EIF1AX突变。有趣的是，与GNAQ/GNA11 Q209L突变相比，GNAQ Q209P突变患者从死亡到死亡的时间更长，这表明GNAQ/GNA11突变类型的差异可能决定了MUM的预后。GNAQ/GNA11蛋白的结构改变及其对MUM患者生存的影响有待进一步研究。
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. More than 90% of UMs harbor mutually exclusive activating mutations in G-proteins. The mutations are early events in UM development and considered to be driver mutations in carcinogenesis. Even after treatment of primary uveal melanoma, up to 50% of patients subsequently develop recurrence, predominantly in the liver. GNAQ mutations are not reported to be correlated to survival, while the mutations in GNA11 are reported more frequently in metastatic UM. We investigated the correlation of survival after development of metastasis (Met-to-Death) of metastatic uveal melanoma (MUM) patients with GNA11 and GNAQ mutations. We identified that MUM with mutation patterns of Q209P vs. Q209L in GNA11 and GNAQ might predict survival of MUM patients. Uveal melanoma is the most common primary ocular malignancy in adults, characterized by gene mutations in G protein subunit alpha q (GNAQ) and G protein subunit alpha 11 (GNA11). Although they are considered to be driver mutations, their role in MUM remains elusive. We investigated key somatic mutations of MUM and their impact on patients’ survival after development of systemic metastasis (Met-to-Death). Metastatic lesions from 87 MUM patients were analyzed by next generation sequencing (NGS). GNA11 (41/87) and GNAQ (39/87) mutations were most predominantly seen in MUM. Most GNA11 mutations were Q209L (36/41), whereas GNAQ mutations comprised Q209L (14/39) and Q209P (21/39). Epigenetic pathway mutations BAP1 (42/66), SF3B1 (11/66), FBXW7 (2/87), PBRM1 (1/66), and SETD2 (1/66) were found. No specimen had the EIF1AX mutation. Interestingly, Met-to-Death was longer in patients with GNAQ Q209P compared to GNAQ/GNA11 Q209L mutations, suggesting the difference in mutation type in GNAQ/GNA11 might determine the prognosis of MUM. Structural alterations of the GNAQ/GNA11 protein and their impact on survival of MUM patients should be further investigated.
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影响因子：
5.2
作者：
Chacón M;Pfluger Y;Angel M;Waisberg F;Enrico D
通讯作者：
Enrico D
影响因子：
8.8
作者：
Hughes, S;Damato, BE;Houlston, RS
通讯作者：
Houlston, RS
影响因子：
30.8
作者：
Moore, Amanda R.;Ceraudo, Emilie;Sher, Jessica J.;Guan, Youxin;Shoushtari, Alexander N.;Chang, Matthew T.;Zhang, Jenny Q.;Walczak, Edward G.;Kazmi, Manija A.;Taylor, Barry S.;Huber, Thomas;Chi, Ping;Sakmar, Thomas P.;Chen, Yu
通讯作者：
Chen, Yu
DOI：
10.1158/1541-7786.mcr-17-0007
发表时间：
2017-05
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Chua V;Lapadula D;Randolph C;Benovic JL;Wedegaertner PB;Aplin AE
通讯作者：
Aplin AE
影响因子：
16.6
作者：
Field MG;Durante MA;Anbunathan H;Cai LZ;Decatur CL;Bowcock AM;Kurtenbach S;Harbour JW
通讯作者：
Harbour JW