鉴定肺腺癌中高频、高危和高表达的突变基因。
Identification of mutant genes with high-frequency, high-risk, and high-expression in lung adenocarcinoma.
机构信息
Department of Oncology, Tongji Hospital, Tongji University School of Medicine Shanghai, China.
Department of Clinical Laboratory Medicine, Tongji Hospital, Tongji University School of Medicine Shanghai, China.
出版信息
Thorac Cancer. 2014 May;5(3):211-8. doi: 10.1111/1759-7714.12080. Epub 2014 Apr 22.
BACKGROUND
To identify mutant genes with high-frequency-risk-expression between lung adenocarcinoma and normal samples.
METHODS
The ribonucleic acid RNA-Seq data GSE34914 and GSE37765 were downloaded from the Gene Expression Omnibus database, including 12 lung adenocarcinoma samples and six controls. All RNA-Seq reads were processed and the gene-expression level was calculated. Single nucleotide variation (SNV) was analyzed and the locations of mutant sites were recorded. In addition, the frequency and risk-level of mutant genes were calculated. Gene Ontology (GO) functional analysis was performed. The reported cancer genes were searched in tumor suppressor genes, Cancer Genes, and the Catalogue of Somatic Mutations in Cancer (COSMIC) database.
RESULTS
The SNV annotations of somatic mutation sites showed that 70% of mutation sites in the exon region occurred in the coding sequence (CDS). Thyroid hormone receptor interactor (TRIP)12 was identified with the highest frequency. A total of 118 mutant genes with high frequency and high-risk were selected and significantly enriched into several GO terms. No base mutation of cyclin C (CCNC) or RAB11A was recorded. At fragments per kilobase per million reads (FPKM) ≥ 56.5, reported tumor suppressor genes catenin (cadherin-associated protein), delta (CTNND)1, dual specificity phosphatase (DUSP)6, malate dehydrogenase (MDH)1 and RNA binding motif protein (RBM)5, were identified. Notably, signal transducer and activator of transcription 2 (STAT2) was the only transcription factor (TF) with high-risk mutation and its expression was detected.
CONCLUSION
For the mutant genes with high-frequency-risk-expression, CTNND1, DUSP6, MDH1 and RBM5 were identified. TRIP12 might be a potential cancer-related gene, and expression of TF STAT2 with high-risk was detected. These mutant gene candidates might promote the development of lung adenocarcinoma and provide new diagnostic potential targets for treatment.
背景
鉴定肺腺癌与正常样本间高频风险表达的突变基因。
方法
从基因表达综合数据库中下载 RNA-Seq 数据 GSE34914 和 GSE37765，包括 12 例肺腺癌样本和 6 例对照。所有 RNA-Seq 读段均经过处理，并计算基因表达水平。分析单核苷酸变异（SNV），记录突变位点的位置。此外，还计算了突变基因的频率和风险水平。进行基因本体论（GO）功能分析。在肿瘤抑制基因、癌症基因和癌症体细胞突变目录（COSMIC）数据库中查找报道的癌症基因。
结果
体细胞突变位点的 SNV 注释显示，外显子区域的突变位点有 70%发生在编码序列（CDS）中。甲状腺激素受体相互作用蛋白（TRIP）12 的出现频率最高。共筛选出 118 个高频、高危的突变基因，并显著富集到几个 GO 术语中。未记录到细胞周期蛋白 C（CCNC）或 RAB11A 的碱基突变。在每百万读段每千碱基片段数（FPKM）≥56.5 时，鉴定出报道的肿瘤抑制基因连环蛋白（钙黏蛋白相关蛋白）、δ（CTNND）1、双特异性磷酸酶（DUSP）6、苹果酸脱氢酶（MDH）1 和 RNA 结合基序蛋白（RBM）5。值得注意的是，信号转导和转录激活因子 2（STAT2）是唯一具有高危突变的转录因子（TF），并检测到其表达。
结论
对于高频风险表达的突变基因，鉴定出 CTNND1、DUSP6、MDH1 和 RBM5。TRIP12 可能是一个潜在的癌症相关基因，并且检测到具有高危的 TF STAT2 的表达。这些候选突变基因可能促进肺腺癌的发展，并为治疗提供新的潜在诊断靶点。
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