Sundaresan Varsha, Lin Victor T, Liang Faming, Kaye Frederic J, Kawabata-Iwakawa Reika, Shiraishi Kouya, Kohno Takashi, Yokota Jun, Zhou Lei
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA; UF Health Cancer Center, University of Florida, Gainesville, FL, USA.
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA.
Cancer Genet. 2017 Oct;216-217:20-28. doi: 10.1016/j.cancergen.2017.05.003. Epub 2017 Jun 7.
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and demands effective targeted therapeutic strategies. In this meta-analysis study, we aim to identify significantly mutated genes and regulatory pathways to help us better understand the progression of SCLC and to identify potential biomarkers. Besides ranking genes based on their mutation frequencies, we sought to identify statistically significant mutations in SCLC with the MutSigCV software. Our analysis identified several genes with relatively low mutation frequency, including PTEN, as highly significant (p < 0.001), suggesting these genes may play an important role in the progression of SCLC. Our results also indicated mutations in genes involved in the axon guidance pathways likely play an important role in SCLC progression. In addition, we observed that the mutation rate was significantly higher in samples with RB1 gene mutated when compared to samples with wild type RB1, suggesting that RB1 status has significant impact on the mutation profile and disease progression in SCLC.
小细胞肺癌（SCLC）约占所有肺癌的15%，需要有效的靶向治疗策略。在这项荟萃分析研究中，我们旨在识别显著突变的基因和调控通路，以帮助我们更好地理解SCLC的进展，并识别潜在的生物标志物。除了根据基因的突变频率进行排名外，我们还试图使用MutSigCV软件识别SCLC中具有统计学意义的突变。我们的分析确定了几个突变频率相对较低的基因，包括PTEN，具有高度显著性（p < 0.001），表明这些基因可能在SCLC的进展中起重要作用。我们的结果还表明，轴突导向通路相关基因的突变可能在SCLC进展中起重要作用。此外，我们观察到，与野生型RB1样本相比，RB1基因发生突变的样本中的突变率显著更高，这表明RB1状态对SCLC的突变谱和疾病进展有显著影响。
