EUR J Cancer:657例黑色素瘤患者NRAS的增益分析并评估其对MEK抑制剂的敏感性

2017-12-24 MedSci MedSci原创

神经母细胞瘤基因(NRAS)突变在中国黑色素瘤患者中已经得到了描述。 然而,NRAS基因突变的临床意义尚未经过大规模调查。一项临床研究共纳入了657个黑色素瘤样本。 使用QuantiGene Plex DNA分析检查NRAS的拷贝数,同时评价了含有NRAS增益的细胞系和患者衍生的异种移植物(PDX)模型对MAP / ERK激酶(MEK)抑制剂()的敏感性。 NRAS的总增益率为14.0%(9

神经母细胞瘤基因(NRAS)突变在中国黑色素瘤患者中已经得到了描述。 然而,NRAS基因突变的临床意义尚未经过大规模调查。一项临床研究共纳入了657个黑色素瘤样本。 使用QuantiGene Plex DNA分析检查NRAS的拷贝数,同时评价了含有NRAS增益的细胞系和患者衍生的异种移植物(PDX)模型对MAP / ERK激酶(MEK)抑制剂()的敏感性。

NRAS的总增益率为14.0%92/657)。 NRAS增益发生率在肢端,黏膜,慢性日光损伤(CSD)和非CSD黑素瘤中的表达率分别为12.2%15.8%9.5%19.4% NRAS增益与NRAS突变是相互排斥的(P<0.036)。NRAS增益的黑色素瘤患者的中位生存时间比正常NRAS拷贝数的患者显著缩短(P<0.006)。对于包含NRAS增益的患者,较高拷贝数的中位生存时间显著短于较低拷贝数者。而MEK抑制剂(binimetinib)能够抑制NRAS增益的PDX模型的增长。

结果显示,NRAS增益在黑色素瘤患者中的频繁发生可能预示黑色素瘤的不良预后。但值得庆幸的是,含有NRAS增益的黑色素瘤细胞和PDX模型对MEK抑制剂(binimetinib)敏感。

 

原始出处:

Yan, Junya, et al. "Analysis of NRAS gain in 657 patients with melanoma and evaluation of its sensitivity to a MEK inhibitor." European Journal of Cancer 2018 89: 90-101. doi.org/10.1016/j.ejca.

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    2018-04-10 naiwu77
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    2018-09-17 sunylz
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    2018-04-13 tcm99hq
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    2018-03-06 jklm09
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背景:黑色素瘤是一种由皮肤和其他器官黑素细胞产生的肿瘤,表现为色素性皮损在数月或数年中发生明显改变。临床症状包括出血、瘙痒、压痛、溃疡等,其恶性程度高,转移发生早,死亡率高。全球每年有数以万计的人罹患这种疾病,其发病率攀升的速度比所有其他类型的实体瘤都要快。尽管人们认为黑色素瘤通常是由于过多的太阳紫外线照射引起的。但日晒和黑色素瘤之间的关联并不像看起来那样简单。对不同年龄和性别的黑色素瘤患者而言,