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Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapyстатья Исследовательская статья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Cheng Hua, Ziyan Guo, Xiaoyu Zhang, Xiao-Jin Wang, Li Zizhang, Wen-Wen Huo, Hong-Cheng Zhong, Li Xiao-Jian, Xiang-Wen Wu, Li Wen-Hao, Zhuo-Wen Chen, Tian-Chi Wu, Xiang-Feng Gan, Bei-Long Zhong, Vassily Lyubetsky, Leonid Rusin, Junnan Yang, Qiyi Zhao, Qing-Dong Cao, Jian-Rong Yang
- Журнал: Journal of Genetics and Genomics
- Том: 50
- Номер: 5
- Год издания: 2023
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 330
- Последняя страница: 340
- DOI: 10.1016/j.jgg.2022.11.005
- Аннотация: 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 performed 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 revealed that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient were as genetically diverse as those from different patients, while within-tumor genetic heterogeneity was significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample showed a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there was no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggests 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.
- Добавил в систему: Любецкий Василий Александрович