The Study Of Lung Cancer In XuanWei Revealed By Whole Genome And Exome Sequencing

ObjectiveLung cancer has the highest incidence and mortality rate among all types of cancers in the world, resulting in more annual deaths than breast, prostate and coloretal cancers combined. Because of non-specific clinical symptoms and lack of measures of detection early stage of lung cancer, most patients are diagnosed in late of lung cancer, that is, incurable stages and disappointing therapeutic regimens, resulting in poor prognosis. Notably, the incidence of lung cancer exceed the worldwide averge drastically in the XuanWei, China. The incidence of female is the most highest in the world. Recent cancer sequencing efforts have used next-generation sequencing technology to provide a genome-wide view of mutations in cancers. Here we performed whole genome sequencing and whole exome sequencing on patients in Xuanwei County with lung cancer to analyze the genomic features. Meanwhile, it is to make a better understand the molecular mechaniasm undelying the XuanWei lung cancer tumongenesis.Methods1. Specimens of XuanWei lung cancer and corresponding pericarcinomatous tissue of operation resction came from department of pathology of Kunming Medical University First Hospital.2. Sequencing of the samples was performed using unchained combinatorial probe anchor ligation (cPAL) chemistry on arrays of self-assembling DNA nanoballs (DNBs).3. Analying the mutations by biomedical software and significant enrichment of GO terms, aimiing at found key genes or pathways related to the disease, the molecular mechnisam underlying the XuanWei lung cancer carcinogensis was established.4. Sequencing of the samples was performed using Agilent SureSelect Human All Exon 51Mb(V4).5. Correlation analysis of candidate variation genes with clinical data,and characteristics of candidate genes function、pathway、biological process and6. tissue distribution online. Comprehensive understanding of the mechanism of candidate genes in Xuanwei lung cancer.Results1.1. Whole genome sequencing was performed on lung tumor (80×coverage) and adjacent normal tissue (80×), where over 95% of sequencing reads were mapped to the reference genome covering more than 97% of the bases. A total of 181,303 and149,844 somatic mutations were detected in the tumor genomes. The lung cancer in Xuanwei genome had a remarkably high proportion of CG-AT transversions, which is the most common substitution in smokers with lung cancer. Somatic variations in tumors were identified by comparing the variant calls in the tumor with the corresponding normal genomes,34 somatic SNPs,64 somatic Indels and 82 somatic SVs were discovered.2. GO analysis of Pathyway analysis suggested the involvement of wide-ranging cancer-related processes, including signal transduction, cell division, cell adhesion, regulation of cell proliferation and activation of MAPK activity. In addition, pathway analysis suggested that cell cycle, regulation of actin cytoskeleton, MAPK signaling pathway, Calcium signaling pathway, non-small cell lung cancer and Wnt signaling pathway were involved in.3. Whole exome sequencing was performed on 20 lung adenocarcinoma tumor tissues, result in 304928 SNPs and 40359 Indels, of which 89239 mutations were novel. After analysis there is 7 same genes with mutations.4. We identified 13 genes associated xuanwei lung cancer, PRKCZwere not reported have association with lung cancer before. Candidate genes mutations were relevant with clinical data, and we also identified relationship networks between the candidate genes, their functions and biological processes or pathways play an important role in the occurrence and development of tumors.ConclusionsOur study suggested that gene mutations might be potentially important for the Xuanwei lung cancer, they play an important role in the occurrence and development of Xuanwei lung cancer, and they might be used as a genetic marker to locate with Xuanwei population.