Comparison Of Genetic Mutation Status Between Plasma And Tumor Tissue In ?A-? Stage Non-small Cell Lung Cancer Patients

Background:Lung cancer is a malignant tumor with the highest morbidity and mortality in China.In the era of precision medical treatment with the continuous development of genetic technology,the tumor genotyping plays extremely important role in the lung cancer patients'clinical diagnosis and treatment.The circulating tumor DNA(ctDNA)isolated from plasma has a great potential to identify gene mutations in the non-small cell lung cancer(NSCLC)patients.The evaluation of the diagnostic capacity of ctDNA total variability includes single nucleotide variation(SNV),insertion and deletion(indels)and gene recombination.ctDNA testing also called liquid biopsy,is a non-invasive detection,which is to avoid the inherent defects of the tissue biopsy.However,the next generation sequencing(NGS)has not been widely used to test the gene mutation of plasma ctDNA.Method:We matched tissue and plasma specimens from 39 Chinese patients with advanced non-small cell lung cancer,staging from IIIB to IV based on the 8~thh edition ofUnion for International Cancer Control(UICC)lung cancer stage.Pathological tissues were obtained from surgery or biopsy.We use Illumina HiSeq platform to perform the NGS testing of plasma and tissue.Meanwhile,we improved the traditional sequencing methods.The verification experiments were performed on fusion gene mutation and ultra-lower frequency mutation using common clinical technologies,including FISH,Sanger sequencing and immunohistochemistry.Results:There are 20 females and 19 males in the 39 patients,all diagnosed as NSCLC of stage IIIA or IV.Among them,34 cases(87%)are adenocarcinoma and 5cases(13%)are squamous cell carcinoma.Both the tissue DNA mutation and plasma ctDNA mutation are detected in 18 patients(47.43%),but in 12 patients(30.27%)no somatic mutation is detected in tissue or blood samples.Genetic mutations are found in 8 patients'(21.80%)tissue specimens but not in blood.The overall consistency between tissue DNA mutation and plasma ctDNA mutation is 78.21%.The sensitivity of detecting plasma ctDNA mutation and genetic recombination of Epidermal Growth Factor Receptor(EGFR),KRAS,PIK3CA are 70.6%,75%,50%,70%and 60%respectively.Conclusion:Plasma ctDNA may be an effective source to detect cancer-related genetic mutation in advanced NSCLC patients.The ctDNA targeted sequencing provides a promising future for the accurate diagnosis,which will be a viable option for clinical monitoring of NSCLC patients.