Lung Adenocarcinoma Promotion by Air Pollutants Whole Genome Sequencing. Lung Adenocarcinoma Promotion by Air Pollutants Whole Genome Sequencing

A complete understanding of how environmental carcinogenic exposures promote cancer formation is lacking. Over 70 years ago, tumour formation was proposed to occur in a two step process: an initiating step which induces mutations in normal tissue, followed by a promoter step which triggers cancer development. Recent evidence has revealed healthy human tissue contains a patchwork of clones harbouring oncogenic mutations.This led us to hypothesise that environmental particulate matter measuring PM2.5, known to be associated with lung cancer risk, might promote lung cancer by acting on pre-existing cells harbouring oncogenic mutations in normal lung tissue. Here we use a combination of WGS and RNA-seq of mouse tumours from pollution-exposed mice to examine the impact of particulate matter on mutagenesis and gene expression respectively.

目前学界对环境致癌暴露如何促进癌症发生的完整机制仍缺乏清晰认知。七十余年前，有研究提出肿瘤发生遵循两步进程：首先为启动阶段，可诱导正常组织产生基因突变；随后为促癌阶段，触发癌症的发展进程。近年的研究证据显示，健康人体组织中存在由携带致癌突变的克隆细胞构成的嵌合斑块。基于上述发现，我们提出假说：已知与肺癌风险密切相关的PM2.5（细颗粒物），或可通过作用于正常肺组织中已携带有致癌突变的细胞，进而促进肺癌的发生。本研究通过对暴露于污染环境的小鼠肿瘤样本开展全基因组测序（WGS）与转录组测序（RNA-seq）联合分析，分别探究颗粒物对诱变过程及基因表达的影响。