生物
肺癌
癌症治疗
小学(天文学)
趋同(经济学)
癌症
计算生物学
遗传学
内科学
医学
物理
天文
经济
经济增长
作者
Hua Cheng,Ziyan Guo,Xiaoyu Zhang,Xiaojin Wang,Zizhang Li,Wenwen Huo,Hongcheng Zhong,Xiaojian Li,Xia Wu,Wenhao Li,Zhuo-Wen Chen,Tian-Chi Wu,Xiangfeng Gan,Beilong Zhong,Vassily Lyubetsky,L.Y. Rusin,Jun Yang,Qiyi Zhao,Qingdong Cao,Jinfu Yang
标识
DOI:10.1016/j.jgg.2022.11.005
摘要
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.
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