Genomic characterisation of pulmonary subsolid nodules: mutational landscape and radiological features
Genomic characterisation of pulmonary subsolid nodules: mutational landscape and radiological features
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肺亚实性结节的基因组特征：突变景观和放射学特征
DOI：
10.1183/13993003.01409-2019
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发表时间：
2020-02-01
影响因子：
24.3
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Li, Yanmeng;Li, Xiao;Wang, Jun
背景资料：肺腺癌（LUAD）的放射学表现为亚实性结节（SSN）表现出更多的惰性比固体LUAD的生物学行为。SSN通常包括浸润前和浸润性早期腺癌，可分为纯磨玻璃结节和部分实性结节。SSNs.Methods的基因组特征仍然知之甚少：我们进行了154 SSN样本从120治疗初治的中国患者全外显子组测序。收集这些SSN的临床参数和放射学特征。定义了SSN的基因组景观以及与高级LUAD的差异。此外，我们研究了多灶性SSN的肿瘤内异质性和克隆关系，并进行了放射基因组学分析，以将SSN的成像和分子特征联系起来。Fisher精确和Wilcoxon秩和检验用于统计分析。结果：整个SSN队列的中位体细胞突变率为1.12突变每Mb。EGFR突变是最突出和最显著的变异，其次是RBM10、TP53、STK11和KRAS突变。SSN和晚期LUAD在基因组水平上的差异被解开。SSN的分支进化和显著的基因组异质性。虽然多中心起源占主导地位，我们也发现早期转移事件之间的多灶性SSN。使用放射基因组学分析，我们发现，较高的比例固体成分的SSN伴随着显着较高的突变频率在EGFR，TP53，RBM10和ARID1B，这表明这些基因发挥作用的LUADs.Conclusions的进展：我们的研究提供了第一个全面的描述突变景观和放射基因组学映射的SSN。
Background: Lung adenocarcinomas (LUADs) that display radiologically as subsolid nodules (SSNs) exhibit more indolent biological behaviour than solid LUADs. SSNs, commonly encompassing pre-invasive and invasive yet early-stage adenocarcinomas, can be categorised as pure ground-glass nodules and partsolid nodules. The genomic characteristics of SSNs remain poorly understood.Methods: We subjected 154 SSN samples from 120 treatment-naive Chinese patients to whole-exome sequencing. Clinical parameters and radiological features of these SSNs were collected. The genomic landscape of SSNs and differences from that of advanced-stage LUADs were defined. In addition, we investigated the intratumour heterogeneity and clonal relationship of multifocal SSNs and conducted radiogenomic analysis to link imaging and molecular characteristics of SSNs. Fisher's exact and Wilcoxon rank sum tests were used in the statistical analysis.Results: The median somatic mutation rate across the SSN cohort was 1.12 mutations per Mb. Mutations in EGFR were the most prominent and significant variation, followed by those in RBM10, TP53, STK11 and KRAS. The differences between SSNs and advanced-stage LUADs at a genomic level were unravelled. Branched evolution and remarkable genomic heterogeneity were demonstrated in SSNs. Although multicentric origin was predominant, we also detected early metastatic events among multifocal SSNs. Using radiogenomic analysis, we found that higher ratios of solid components in SSNs were accompanied by significantly higher mutation frequencies in EGFR, TP53, RBM10 and ARID1B, suggesting that these genes play roles in the progression of LUADs.Conclusions: Our study provides the first comprehensive description of the mutational landscape and radiogenomic mapping of SSNs.