Al analysis, writing–original draft, and visualization. XW: methodology, formal evaluation, writing–original draft, and visualization. YS: methodology, formal analysis, writing–original draft, and visualization. XZ: conceptualization, methodology, validation, investigation, sources, writing–original draft, supervision, project administration, and funding acquisition. The authors study and authorized the final manuscript. Funding This study was supported by the National All-natural Science (81302009). Availability of information and components The information generated in this study are accessible within the article and its supplementary information files. The raw sequencing data will not be publicly accessible because of privacy or ethical restrictions but are accessible upon reasonable request in the corresponding author.Conclusions In conclusion, by performing a large-scale evaluation in 1025 compound EGFR mutation-positive NSCLC patients, we discovered that distinctive subtypes of compound EGFR mutations were associated with distinct demographic options, co-mutated genes, mutational signatures, and chromosomal instability levels, also as distinguishing prognosis to first-line EGFR TKIs. Our study assists improved have an understanding of the clinical qualities of compound EGFR mutations and emphasizes the value of determining the specific kinds of EGFR mutations, which can potentially direct prognosis prediction and provide personalized treatment options to NSCLC patients.Abbreviations 19-Del Short in-frame deletions in exon 19 20ins Exon 20 insertions ADC Lung adenocarcinoma ASC Adenosquamous carcinoma from the lung CIS Chromosome instability score EGFR Epidermal development issue receptor ExAC Exome aggregation consortium FFPE Formalin-fixed paraffin-embedded IGV Integrative genomics viewer JM Juxtamembrane domain KD Kinase domain LOH Loss-of-heterozygosity MAF Mutant allele frequency mPFS Median progression-free survival NGS Next-generation sequencing NSCLC Non-small cell lung cancer PD Progressive disease PD-L1 Programmed death-ligand 1 PFS Progression-free survival SCC Lung squamous cell carcinoma SNVs Single-nucleotide variations TKI Tyrosine kinase inhibitor TM Transmembrane domain TMB Tumor mutational burden VUS Variant of uncertain significanceDeclarationsEthics approval and consent to participate This study was authorized by the Ethics Committee in the Fudan University Shanghai Cancer Center, Shanghai Cancer Center Institutional Evaluation Board (SCCIRB), and in accordance together with the Declaration of Helsinki (ethics approval number: 20042169-2005). Informed consent was obtained from each of the participating sufferers.LIF Protein Storage & Stability All sufferers offered written informed consent to participate and publication.CCL1 Protein supplier Consent for publication Not applicable.PMID:23577779 Zhao et al. BMC Medicine(2023) 21:Web page 15 ofCompeting interests YX, QW, CL, JCY, QO, XW, and YS are personnel of Nanjing Geneseeq Technology Inc. Each of the remaining authors declare that they have no competing interests. Author facts 1 Division of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. 2 Department of Oncology, Shanghai Health-related College, Fudan University, Shanghai 200032, China. 3 Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China. 4 Department of Respiratory Medicine, Wuxi Branch of Ruijin Hospital, Shanghai Jiao Tong University, Wuxi, Jiangsu 214145, China. 5 Geneseeq Investigation Institute, Nanjing Geneseeq Technology Inc, Nanjing 210032, Jiangsu, China. 6 College of Public Wellness, Nanjing Health-related U.
