美国Luc G. T. Morris课题组的最新研究报道了纵向和多点采样揭示肿瘤在转移传播过程中的突变和拷贝数进化。相关论文于2025年6月2日发表在《自然—遗传学》杂志上。

为了了解癌症转移过程中的遗传进化，课题组人员分析了3,732名癌症患者的基因组图谱，这些患者的几个肿瘤部位进行了纵向活检。在远处转移过程中，观察到肿瘤积累拷贝数改变（CNAs）的程度远高于突变。特别是，全基因组复制的发展是转移过程中的一个常见事件，在28%的患者中重新出现。11%的患者在转移过程中出现9p（包括CDKN2A）缺失。在较小程度上，突变和等位基因丢失在人类白细胞抗原类I和其他与抗原呈递相关的基因也出现了。在接受免疫治疗的患者中，增加CNA而不增加突变负荷与免疫逃避有关。综上所述，这些数据表明，在癌症转移过程中，CNA而不是突变积累更丰富，这可能是由于增强的细胞适应性和免疫原性之间的更有利的平衡。

附：英文原文

Title: Longitudinal and multisite sampling reveals mutational and copy number evolution in tumors during metastatic dissemination

Author: Zhao, Karena, Vos, Joris, Lam, Stanley, Boe, Lillian A., Muldoon, Daniel, Han, Catherine Y., Valero, Cristina, Lee, Mark, Fitzgerald, Conall, Lee, Andrew S., Prasad, Manu, Jain, Swati, Deng, Xinzhu, Chan, Timothy A., Berger, Michael F., Bandlamudi, Chaitanya, Zhou, Xi Kathy, Morris, Luc G. T.

Issue&Volume: 2025-06-02

Abstract: To understand genetic evolution in cancer during metastasis, we analyzed genomic profiles of 3,732 cancer patients in whom several tumor sites were longitudinally biopsied. During distant metastasis, tumors were observed to accumulate copy number alterations (CNAs) to a much greater degree than mutations. In particular, the development of whole genome duplication was a common event during metastasis, emerging de novo in 28% of patients. Loss of 9p (including CDKN2A) developed during metastasis in 11% of patients. To a lesser degree, mutations and allelic loss in human leukocyte antigen classI and other genes associated with antigen presentation also emerged. Increasing CNA, but not increasing mutational load, was associated with immune evasion in patients treated with immunotherapy. Taken together, these data suggest that CNA, rather than mutational accumulation, is enriched during cancer metastasis, perhaps due to a more favorable balance of enhanced cellular fitness versus immunogenicity.

DOI: 10.1038/s41588-025-02204-3

Source: https://www.nature.com/articles/s41588-025-02204-3