Characterization of the genetic mouse model of non-small cells lung cancer p53R172Hdeltag/KrasG12D

Background: Non-small cell lung cancer (NSCLC) accounts for 81% of all cases of lung cancer and they are often fatal because 60% of the patients are diagnosed at an advanced stage. Besides the need for earlier diagnosis, there is a great need for additional effective therapies. In this work we investigated the feasibility of a lung cancer progression mouse model, mimicking features of human aggressive NSCLC cancer, as biological reservoir for potential therapeutic targets and biomarkers. Results:RNA-seq profiling was performed on total RNA extracted from lungs of 30 week-old p53R172Hdeltag/KrasG12D and wild type mice to detect fusion genes and gene/exon-level differential expression associated to the increase of tumor mass. Fusion events were not detected in p53R172Hdeltag/KrasG12D tumors. Differential expression at exon-level detected 33 genes with differential exon usage. The study provides a complete transcription overview of the p53R172Hdeltag/KrasG12D mouse NSCLC model Lung mRNA profiles of 30-week old wild type (WT) and p53R172Hdeltag/KrasG12D mice were generated by deep sequencing, in duplicate using Illumina HiSeq2000.背景：非小细胞肺癌（Non-small cell lung cancer, NSCLC）占所有肺癌病例的81%，且致死率极高，原因在于60%的患者确诊时已处于晚期阶段。除了亟需开展早期诊断之外，临床还迫切需要更多有效的治疗方案。本研究构建了模拟人类侵袭性非小细胞肺癌特征的肺癌进展小鼠模型，并将其作为潜在治疗靶点与生物标志物的生物学储备库，对该模型的可行性展开了探究。结果：本研究针对30周龄p53R172HΔg/KrasG12D小鼠与野生型小鼠的肺组织总RNA开展RNA测序（RNA-seq）谱分析，以检测与肿瘤负荷增加相关的融合基因及基因/外显子水平的差异表达事件。在p53R172HΔg/KrasG12D小鼠的肿瘤组织中未检测到融合事件。外显子水平的差异表达分析共筛选出33个存在外显子使用差异的基因。本研究完整呈现了p53R172HΔg/KrasG12D小鼠非小细胞肺癌模型的转录组全貌。本研究采用Illumina HiSeq2000平台，对30周龄野生型（WT）及p53R172HΔg/KrasG12D小鼠的肺组织mRNA进行双重复样深度测序，获取其转录组谱。