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The Research Of Genetic Mutation And Tumor Mutation Burden Based Of Pulmonary Sarcomatoid Carcinomas On Next-generation Sequencing

Posted on:2019-05-30Degree:MasterType:Thesis
Country:ChinaCandidate:X H LiangFull Text:PDF
GTID:2404330545971808Subject:Internal Medicine
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Objectives: We performed next-generation sequencing on our collection of clinical and pathological characteristics in 32 PSC patients to identify potential driver genes and to identify potentially effective drug targets.The goal of this study was to perform NGS on our collection of clinical and pathological characteristics in 32 PSC patients to identify tumor mutation burden and to identify potentially the use of immunotherapy.Material and Methods: In this study,a group of 32 patients with PSC was studied.We used NGS technology to detect 416 cancer-related genes and tumor mutation burdens in 32 Chinese patients with PSCs.Results: EGFR(28%),KRAS(22%),and MET(16%)are the most commonly mutated oncogenes,while the top mutated tumor suppressor genes are TP53(69%)and RB1(25%).The occurrence of EGFR sensitive mutation was 25% in the patients who had own EGFR mutation.Rare EGFR mutations accounted for 75%.5 of the 32 patients(16%)harbored MET mutations that occurred in exon 14,13 and intron 12.Exon 14 MET mutation rate was 60% in the patients who had own MET mutation.TMB ranged from 7.0 to 45.0 mutations/MB,with a median TMB of 15.0 mutations/MB.In the analysis of the correlation between overall TMB and specific gene mutation,we found that patients mutated in BRCA2,SMARCA4 have significantly higher TMB compared to patients with wide-type genes.Disease stage is the only characteristic that significantly associated with OS(p = 0.004).The presence of KRAS mutation seems to be associated with significantly worse OS(p = 0.004).Conclusion: The next-generation sequencing study of pulmonary sarcomatoid carcinoma showed MET mutations in 16% of cases,EFGR mutations in 28% of cases.A higher TMB were identified in the majority of PSC cases.Tumor staging is an independent factor that affects the prognosis of PSC patients.
Keywords/Search Tags:Pulmonary sarcomatoid carcinoma, Molecular targeted therapy, immunotherapy, tumor mutation burden, MET, next generation sequencing
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