Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer

Pengfei Ma, Yujie Fu, Mei-Chun Cai, Ying Yan, Ying Jing, Shengzhe Zhang, Minjiang Chen, Jie Wu, Ying Shen, Liang Zhu, Hong-Zhuan Chen, Wei-Qiang Gao, Mengzhao Wang, Zhenyu Gu, Trever G. Bivona, Xiaojing Zhao () and Guanglei Zhuang ()
Additional contact information
Pengfei Ma: Shanghai Jiao Tong University
Yujie Fu: Shanghai Jiao Tong University
Mei-Chun Cai: Shanghai Jiao Tong University
Ying Yan: GenenDesign Co., Ltd
Ying Jing: Shanghai Jiao Tong University
Shengzhe Zhang: Shanghai Jiao Tong University
Minjiang Chen: Chinese Academy of Medical Sciences
Jie Wu: The Affiliated Hospital of Qingdao University
Ying Shen: Shanghai Jiao Tong University School of Medicine
Liang Zhu: Shanghai Jiao Tong University School of Medicine
Hong-Zhuan Chen: Shanghai Jiao Tong University School of Medicine
Wei-Qiang Gao: Shanghai Jiao Tong University
Mengzhao Wang: Chinese Academy of Medical Sciences
Zhenyu Gu: GenenDesign Co., Ltd
Trever G. Bivona: University of California
Xiaojing Zhao: Shanghai Jiao Tong University
Guanglei Zhuang: Shanghai Jiao Tong University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract Recent genomic analyses have revealed substantial tumor heterogeneity across various cancers. However, it remains unclear whether and how genomic heterogeneity is constrained during tumor evolution. Here, we sequence a unique cohort of multiple synchronous lung cancers (MSLCs) to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. We find that each multicentric primary tumor harbors distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable. However, functional studies show a strikingly constrained tumorigenic pathway underlying heterogeneous genetic variants. These results suggest that although the mutation-specific routes that cells take during oncogenesis are stochastic, genetic trajectories may be constrained by selection for functional convergence on key signaling pathways. Our findings highlight the robust evolutionary pressures that simultaneously shape the expansion and constraint of genomic diversity, a principle that holds important implications for understanding tumor evolution and optimizing therapeutic strategies.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-00963-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00963-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-00963-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().