Abstract
Abstract Background: Lung cancer approximately accounts for more than a third of cancers, approximately 787,000 in China annually, which the death rate is greatest and most lethal in all cancers. However, clonal evolutionary molecular mechanism of lymphatic metastasis in lung cancer remains largely unknown according to previously reported. Methods: In this study, we systematically analyzed clonal evolution of 21 primary patients paired with lymphatic metastasis based on 500 gene-panel target sequencing and clinical characters. The two pipelines were performed to identify the subclones between primary and lymphatic metastasis on each patient, one is Pyclone, citup and Timespace, another is sciClone and clonevol. Furthermore, the genes associated with clonal evolutions were verified to be differentially mutated genes between primary and lymphatic metastasis in MSK-IMPACT 2017 cohort by fisher-test (P < 0.05). Results: The clonal clusters were explored in 3 of 21 patients (P08, P52, P57) with lung cancer by first pipeline, and 4 (P02, P08, P14 and P84) by second pipeline. The 2 genes TET2 and BRCA2 were identified to be associated with lymphatic metastasis. The mutation frequency of TET2 and BRCA2 were 4.2% and 7.1% in patients with lymphatic metastasis in validation cohort. Conclusions: We described molecular features of lung cancer patients with lymphatic metastasis. TET2 and BRCA2 mutations promoted development and evolution of tumor cells, which were insightful for developing novel therapeutic strategies to inhibit the progress of tumors. Keywords: Clonal Evolutionary, Molecular Mechanism, Lymphatic Metastasis, Lung cancer Citation Format: Nanan Guo, Hongmei Zhao. Clonal evolutionary molecular mechanism of lymphatic metastasis in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5992.
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