Somatic Genomic Mutations In Normal Controls But Not Counterpart Lung Adenocarcinomas And Functional Study

Lung cancer, which owns the highest case fatality rate among cancers,is induced by cigarette smoking, occupational exposure,environmental pollution and gene mutation. According to 2015 Chinese cancer registration report-lung cancer still owns the highest case fatality rate and mortality rate in China. Over the past few decades, lots of efforts have been made on lung cancer therapy including surgery, radiotherapy, chemotherapy and targeted therapy, however, because of the lack of effective diagnose, the five year overall survival rate of patients is only about 15%. Gene mutation, as one of the risk factor of lung cancer, the gene mutation rate is increasing because of the more and more serious air pollution, cellular oncogenesis is becoming more easier. Tumour heterogeneity is one of the hallmarks of lung cancer,investigation of genome changes such as gene mutation can be very helpful for the understanding of lung carcinogenesis. With the rapid development of lung cancer sequencing technology, more gene mutations have been found, like the driver mutations EGFR and KRAS which play an important role in lung carcinogenesis, providing a new direction for early diagnose and targeted therapy.Somatic genomic mutations in tumours are identified by comprehensive genome sequence, the counterpart normal control is exposed to environmental pollutions just like cancer tisues, so we want to know that is there any somatic alteration in counterpart normal control that may play an important part in lung carcinogenesis.We downloaded genomic sequence of tumour tissues and counterpart normal control from TCGA datebase, then we compared CNCs genome sequences with reference human genome, subtracted genomic changes detected in tumor samples and excluded the single nucleotide polymorphisms (SNPs), we estimated the survival of patients using Kaplan-Meier method.The CNCs harbored 0.93 exonic mutations/Mb, most genes shows C:G>T:A transition,and there are 29 genes mutation rate more than 3%. We found that mutations in ZNF511and TMEM184A are associated with favorable prognosis. The function of ZNF511 remians unclear so far.hence, we decided to investigate it by constructed the plasmids containing the wild type and mutated ZNF511 and transfected into HEK-293T cell line, meanwhile we constructed stable ZNF511 transgenic cell lines by lentivirus. We transfected the small interference RNAs into A549 cell line.which has high expression level of ZNF511, to silence the expression of ZNF511, results showed that knockdown of ZNF511 inhibit cell proliferation and may related to pAKT signal pathway.In summary, we analyzed the genomic alterations in counterpart normal control and provided new insight on lung carcinogenesis. and the study of ZNF511 paved the way of subsequent research.