Our laboratory has been performing various researches to discover etiology, make an early diagnosis, decide the best clinical management, and predict the prognosis of thoracic malignant disease. For that, we established a thoracic cancer tissue repository including lung cancer, esophageal cancer, and thymoma. Our research consists of three major platforms: 1. Exploration of new driver mutations in thoracic malignancies 2. The development of cancer panels 3. The establishment of organoids and analysis of spatial transcriptomes We have previously conducted whole-transcriptome and whole-exome sequencing of adenocarcinoma of the lung and discovered novel gene fusion of KIF5B-RET for the first time in the world. Subsequently, we developed a FISH probe to diagnose KIF5B-RET gene fusion and validated its function in the clinical setting. By analyzing many fusion gene cancer genomes, we investigated the mechanism of fusion gene generation. We found that the majority of fusion gene was generated by complex rearrangement process. Interestingly, those oncogenic gene fusions seemed to occur several decades before the diagnosis of lung cancer. Those discoveries were published on the Cell. We previously analyzed whole transcriptome sequencing results of squamous cell carcinoma and adenocarcinoma of the lung and found they clustered according to the stromal immune profiles. Such findings drove us to investigate the genomic characteristics further to predict immune checkpoint inhibitors. We performed NGS analyses of the genome and transcriptome of the tissue obtained from the patients whose responsiveness to the immune checkpoint inhibitors was known. To establish tailored treatment platforms according to the genomic alteration of cancer, we developed a lung cancer panel that is currently on clinical service in Seoul National University Hospital. We have been working on establishing a lung organoid protocol. Meanwhile, the COVID-19 pandemic took place, and we conducted an exposure study of lung organoids to the coronavirus (SARS-CoV-2). We discovered the mechanism of viral invasion to the lung alveolar cells, its replication characteristics resulting in cellular loss of function. The result was published in Cell Stem Cell. Globally, we participated in an international research consortium of female non-smoking lung cancer and conducted various GWAS studies. Recently we started to collaborate with NCI in the States to conduct another GWAS study of lung cancer. Hopefully, with our research, we can establish the best treatment algorithm for the improved long-term survival of patients who are suffering from thoracic malignant disease.