Translational Medicine Research Institute, Guangzhou Huayin Medical Laboratory Center Co., Ltd., Guangzhou, China.
Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Bioengineered. 2021 Dec;12(1):791-802. doi: 10.1080/21655979.2021.1890382.
The knowledge of genetic variation in Chinese patients with non-small-cell lung cancer (NSCLC) is still limited. We aimed to profile this genetic variation in 206 Chinese patients with NSCLC using next-generation sequencing. Tumor tissues or whole-blood samples were collected and subjected to whole-exome targeted next-generation sequencing, which included 565 tumor-associated genes, for somatic gene mutation screening and copy number variation (CNV) detection. Potential functions of most commonly mutated genes and genes with CNV were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Atotal of 18,749 mutations were identified using targeted next-generation sequencing, and 85.3% of them were missense mutations. Among the mutation, conversions between pyrimidine and purine were predominant, and C> T/G > A was the most common substitution type. High frequencies of mutations were noted in TP53 (47.6%), EGFR (41.7%), CREBBP (23.1%), KMT2C (16.9%), MUC2 (16.6%), DNMT3A (15.5%), LRP1B (15.5%), MUC4 (15.5%), CDC27 (15.2%), and KRAS (12.8%). EGFR and KRAS mutations were mutually exclusive. The tumor mutation load showed differences depending on gender and tumor type. CNV analysis showed that BCORL1 and ARAF have the highest copy number amplification, whereas KDM6A and RBM10 showed the highest copy number deletion. GO and KEGG analyses indicated that high-frequency mutations and CNV genes were concentrated in tumor-related PI3K-Akt, FoxO, and Ras signaling pathway. Cumulatively, we studied somatic gene mutations involved in NSCLC and predicted their clinical significance in Chinese population. These findings may provide clues for etiology and drug target of NSCLC.
中国非小细胞肺癌（NSCLC）患者的遗传变异知识仍然有限。我们旨在通过下一代测序（NGS）对 206 例 NSCLC 患者的这种遗传变异进行分析。收集肿瘤组织或全血样本，并进行全外显子靶向 NGS，包括 565 个肿瘤相关基因，用于体细胞基因突变筛选和拷贝数变异（CNV）检测。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析预测最常见突变基因和具有 CNV 的基因的潜在功能。通过靶向 NGS 共鉴定了 18749 个突变，其中 85.3%为错义突变。在这些突变中，嘧啶和嘌呤之间的转换占主导地位，C>T/G>A 是最常见的取代类型。TP53（47.6%）、EGFR（41.7%）、CREBBP（23.1%）、KMT2C（16.9%）、MUC2（16.6%）、DNMT3A（15.5%）、LRP1B（15.5%）、MUC4（15.5%）、CDC27（15.2%）和 KRAS（12.8%）的突变频率较高。EGFR 和 KRAS 突变相互排斥。肿瘤突变负荷因性别和肿瘤类型而异。CNV 分析显示 BCORL1 和 ARAF 的拷贝数扩增最高，而 KDM6A 和 RBM10 的拷贝数缺失最高。GO 和 KEGG 分析表明，高频突变和 CNV 基因集中在肿瘤相关的 PI3K-Akt、FoxO 和 Ras 信号通路中。综上所述，我们研究了非小细胞肺癌中涉及的体细胞基因突变，并预测了它们在中国人群中的临床意义。这些发现可能为非小细胞肺癌的病因学和药物靶点提供线索。
