Abstract:
Around 80 to 85% of all lung cancers are non-small cell lung cancer (NSCLC). Previous research has aimed at exploring the genetic basis of NSCLC through individual approaches, but studies have yet to investigate the results of combining them. Here we show that analyzing NSCLC genetics through three approaches simultaneously creates unique insights into our understanding of the disease. Through a combination of previous research and bioinformatics tools, we determined 35 NSCLC candidate genes. We analyzed these genes in 3 different approaches. First, we found the gene fusions between these candidate genes. Second, we found the common superfamilies between genes. Finally, we identified mutational signatures that are possibly associated with NSCLC. Each approach has its individual, unique results. Fusion relationships identify specific gene fusion targets, common superfamilies identify possible avenues to determine novel target genes, and identifying NSCLC associated mutational signatures has diagnostic and prognostic benefits. Combining the approaches, we found that gene CD74 has significant fusion relationships, but it has no association with the other two approaches, suggesting that CD74 is associated with NSCLC mainly because of its fusion relationships. Targeting the gene fusions of CD74 may be an alternative NSCLC treatment. This genetic analysis has indeed created unique insight into NSCLC genes. Both the results from each of the approaches separately and combined allow pursuit of more effective treatment strategies for this cancer. The methodology presented can also apply to other cancers, creating insights that current analytical methods could not find.
摘要:
所有肺癌中约有80%至85%是非小细胞肺癌(NSCLC)。先前的研究旨在通过个体方法探索NSCLC的遗传基础,但是研究尚未调查将它们结合起来的结果。在这里,我们表明通过三种方法分析NSCLC遗传学同时为我们对疾病的理解创造了独特的见解。通过结合以前的研究和生物信息学工具,我们确定了35个NSCLC候选基因。我们用3种不同的方法分析了这些基因。首先,我们发现了这些候选基因之间的基因融合。第二,我们发现了基因之间常见的超家族。最后,我们确定了可能与NSCLC相关的突变特征.每种方法都有其个人,独特的结果。融合关系确定特定的基因融合靶标,常见的超家族确定了确定新靶基因的可能途径,鉴定NSCLC相关突变特征具有诊断和预后益处。结合这些方法,我们发现CD74基因具有显著的融合关系,但它与其他两种方法无关,提示CD74与NSCLC主要是由于其融合关系。靶向CD74的基因融合可能是另一种NSCLC治疗方法。这种遗传分析确实创造了对NSCLC基因的独特见解。来自每种方法的单独和组合的两种结果允许对这种癌症寻求更有效的治疗策略。提出的方法也可以适用于其他癌症,创造当前分析方法找不到的见解。