SCI
22 Apr 2020
Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma
Shih David J H,Nayyar Naema,Bihun Ivanna et al. Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma.[J] .Nat. Genet., 2020, 52: 371-377.
Brain metastases from lung adenocarcinoma (BM-LUAD) frequently cause patient mortality. To identify genomic alterations that promote brain metastases, we performed wholeexome sequencing of 73 BM-LUAD cases. Using case-control analyses, we discovered candidate drivers of brain metastasis by identifying genes with more frequent copy-number aberrations in BM-LUAD compared to 503 primary LUADs.
肺腺癌引起的脑转移（BM-LUAD）通常会导致患者死亡。为了鉴定促进脑转移的基因组改变，我们对73例BM-LUAD病例进行了全基因组测序。使用病例对照分析，我们通过鉴定与503个原发性LUAD相比在BM-LUAD中具有更频繁的拷贝数畸变的基因发现了脑转移的候选驱动因素。
We identified three regions with significantly higher amplification frequencies in BM-LUAD, including MYC (12 versus 6%), YAP1 (7 versus 0.8%) and MMP13 (10 versus 0.6%), and significantly more frequent deletions in CDKN2A/B (27 versus 13%). We confirmed that the amplification frequencies of MYC, YAP1 and MMP13 were elevated in an independent cohort of 105 patients with BM-LUAD.
我们在BM-LUAD中鉴定出三个扩增频率明显较高的区域，包括MYC（12对6％），YAP1（7对0.8％）和MMP13（10对0.6％），以及CDKN2A / B的缺失频率更高（27）。则为13％）。我们证实，在105例BM-LUAD患者的独立队列中，MYC，YAP1和MMP13的扩增频率升高。
Functional assessment in patient-derived xenograft mouse models validated the notion that MYC, YAP1 or MMP13 overexpression increased the incidence of brain metastasis. These results demonstrate that somatic alterations contribute to brain metastases and that genomic sequencing of a sufficient number of metastatic tumors can reveal previously unknown metastatic drivers.
在源自患者的异种移植小鼠模型中的功能评估证实了MYC，YAP1或MMP13过表达会增加脑转移发生率的观点。这些结果表明，体细胞的改变有助于脑转移，而且足够数量的转移性肿瘤的基因组测序可以揭示以前未知的转移驱动因子。
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