Department of Health Sciences Research, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
BMC Med Genomics. 2014 Jun 4;7:32. doi: 10.1186/1755-8794-7-32.
Novel and targetable mutations are needed for improved understanding and treatment of lung cancer in never-smokers.
Twenty-seven lung adenocarcinomas from never-smokers were sequenced by both exome and mRNA-seq with respective normal tissues. Somatic mutations were detected and compared with pathway deregulation, tumor phenotypes and clinical outcomes.
Although somatic mutations in DNA or mRNA ranged from hundreds to thousands in each tumor, the overlap mutations between the two were only a few to a couple of hundreds. The number of somatic mutations from either DNA or mRNA was not significantly associated with clinical variables; however, the number of overlap mutations was associated with cancer subtype. These overlap mutants were preferentially expressed in mRNA with consistently higher allele frequency in mRNA than in DNA. Ten genes (EGFR, TP53, KRAS, RPS6KB2, ATXN2, DHX9, PTPN13, SP1, SPTAN1 and MYOF) had recurrent mutations and these mutations were highly correlated with pathway deregulation and patient survival.
The recurrent mutations present in both DNA and RNA are likely the driver for tumor biology, pathway deregulation and clinical outcomes. The information may be used for patient stratification and therapeutic target development.
为了更好地理解和治疗从不吸烟的肺癌患者，需要新的、可靶向的突变。
通过外显子组和 mRNA-seq 对 27 例从不吸烟的肺腺癌患者及其相应的正常组织进行测序。检测体细胞突变，并与通路失调、肿瘤表型和临床结果进行比较。
尽管每个肿瘤中的 DNA 或 mRNA 中的体细胞突变从数百到数千不等，但两种方法的重叠突变只有数百个。无论是 DNA 还是 mRNA 的体细胞突变数量与临床变量均无显著相关性；然而，重叠突变的数量与癌症亚型相关。这些重叠突变优先在 mRNA 中表达，其等位基因频率在 mRNA 中明显高于 DNA。有 10 个基因（EGFR、TP53、KRAS、RPS6KB2、ATXN2、DHX9、PTPN13、SP1、SPTAN1 和 MYOF）发生了高频突变，这些突变与通路失调和患者生存高度相关。
在 DNA 和 RNA 中都存在的复发性突变可能是肿瘤生物学、通路失调和临床结果的驱动因素。这些信息可用于患者分层和治疗靶点的开发。
