The Research Ot Genetic Mutation Of Micropapillary And Solid Histological Subtypes In Lung Adenocarcinoma Based On Next-generation Sequencing

Objectives:Micropapillary and solid lung adenocarcinoma patients have worse outcome.We explore intrinsic genetic mutations among pathological subtypes,providing basis for clinical treatment.Material and Methods:In this study,we performed targeted sequencing of 10 patients with micropapillary subtype lung adenocarcinoma and 14 patients with solid histological subtypes.NGS were performed using a panel including 520 cancer-related genes.Results:In all,229 variants in 131 genes were detected.Different histological subtypes showed different mutational spectrum.In ten patients with micropapillary subtype,73 variants in 54 genes were detected with an average of 7.3 variants per sample.EGFR was most frequently mutated(90%),one patient showed ERBB2 mutation(10%),one patient showed EGFR mutation and Met copy number amplification simultaneously,ALK/KRAS gene mutation were not identified.In fourteen patients with solid histological subtypes,114 variants in 96 genes were found with an average of 10.3 variants per lesion.The most frequently mutated driver gene was EGFR(50%),followed by EML4-ALK fusion,ALK missense variant,KRAS missense variant,MET copy number amplification,MET missense variant,ERBB2 copy number amplification,ERBB2 missense variant.Solid histological subtype has higher median TMB compared to micropapillary subtype(8.3 vs 6.3 mutations/MB).One patient with solid predominant histology showed EGFR-ALK-/STK11-/TP53+mutations and PD-L1-coding gene amplification.Conclusion:Solid and micropapillary adenocarcinoma subtypes are tumors with a high degree of gene heterogeneity.Micropapillary cases harbor EGFR mutations(90%)and ERBB2 mutations(10%),may well respond to EGFR-TKIs.Solid cases have several kinds of driver mutations and higher TMB,precise treatment based on molecular diagnosis is needed.