Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapy

Hua Cheng; Ziyan Guo; Xiaoyu Zhang; Xiao-Jin Wang; Zizhang Li; Wen-Wen Huo; Hong-Cheng Zhong; Xiao-Jian Li; Xiang-Wen Wu; Wen-Hao Li; Zhuo-Wen Chen; Tian-Chi Wu; Xiang-Feng Gan; Bei-Long Zhong; Vassily A. Lyubetsky; Leonid Yu Rusin; Junnan Yang; Qiyi Zhao; Qing-Dong Cao; Jian-Rong Yang

doi:10.1016/j.jgg.2022.11.005

Volume 50 Issue 5

May 2023

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Article Navigation > Journal of Genetics and Genomics > 2023 > 50(5): 330-340

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Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapy

doi: 10.1016/j.jgg.2022.11.005

a. Department of Thoracic Surgery, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong 519000, China;
b. Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China;
c. Program in Cancer Research, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China;
d. Kharkevich Institute for Information Transmission Problems Russian Academy Sciences, Moscow 127051, Russia;
e. Department of Mathematical Logic and Theory of Algorithms, Faculty of Mechanics and Mathematics, Lomonosov Moscow State University, Moscow 119991, Russia;
f. Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China;
g. Guangdong Provincial Key Laboratory of Liver Disease Research the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China;
h. Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China

Funds:

This work was supported by the National Key Research and Development Program of China to J.-R. Y. (2021YFF1200904 and 2021YFA1302500), the National Natural Science Foundation of China to J.-R. Y. (31871320 and 81830103), and by Science and Technology Planning Project of ZhuHai, China to H. C., and by Science and Technology Planning Project of Guangdong Province, China to X. Z. (2014A030304053).

Received Date: 2022-11-11
Accepted Date: 2022-11-11
Publish Date: 2022-11-19

Abstract

Abstract

Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient are as genetically diverse as those from different patients, while within-tumor genetic heterogeneity is significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there is no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis.
- Multiple primary lung cancer,
- Cancer evolution,
- Convergent evolution

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References(46)

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