AUTHOR=Dong Shao-wei , Li Rong , Cheng Zhiqiang , Liu Dong-cheng , Xia Jinquan , Xu Jing , Li Shixuan , Wang Jian , Yue Yongjian , Fan Yingrui , Cao Yundi , Dai Lingyun , Wang Jigang , Zhao Pan , Wang Xin , Xiao Zhangang , Qiu Chen , Wang Guang-suo , Zou Chang TITLE=Mutational Pattern in Multiple Pulmonary Nodules Are Associated With Early Stage Lung Adenocarcinoma JOURNAL=Frontiers in Oncology VOLUME=10 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.571521 DOI=10.3389/fonc.2020.571521 ISSN=2234-943X ABSTRACT=

The clinical significance of mutation in multiple pulmonary nodules is largely limited by single gene mutation-directed analysis and lack of validation of gene expression profiles. New analytic strategy is urgently needed for comprehensive understanding of genomic data in multiple pulmonary nodules. In this study, we performed whole exome sequencing in 16 multiple lung nodules and 5 adjacent normal tissues from 4 patients with multiple pulmonary nodules and decoded the mutation information from a perspective of cellular functions and signaling pathways. Mutated genes as well as mutation patterns shared in more than two lesions were identified and characterized. We found that the number of mutations or mutated genes and the extent of protein structural changes caused by different mutations is positively correlated with the degree of malignancy. Moreover, the mutated genes in the nodules are associated with the molecular functions or signaling pathways related to cell proliferation and survival. We showed a developing pattern of quantity (the number of mutations/mutated genes) and quality (the extent of protein structural changes) in multiple pulmonary nodules. The mutation and mutated genes in multiple pulmonary nodules are associated with cell proliferation and survival related signaling pathways. This study provides a new perspective for comprehension of genomic mutational data and might shed new light on deciphering molecular evolution of early stage lung adenocarcinoma.