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Thermodynamic energetics underlying genomic instability and whole-genome doubling in cancer.
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2020-08-04 , DOI: 10.1073/pnas.1920870117
Francoise Remacle 1, 2 , Thomas G Graeber 3, 4, 5, 6, 7 , R D Levine 5, 6, 8, 9, 10
Affiliation  

Genomic instability contributes to tumorigenesis through the amplification and deletion of cancer driver genes. DNA copy number (CN) profiling of ensembles of tumors allows a thermodynamic analysis of the profile for each tumor. The free energy of the distribution of CNs is found to be a monotonically increasing function of the average chromosomal ploidy. The dependence is universal across several cancer types. Surprisal analysis distinguishes two main known subgroups: tumors with cells that have or have not undergone whole-genome duplication (WGD). The analysis uncovers that CN states having a narrower distribution are energetically more favorable toward the WGD transition. Surprisal analysis also determines the deviations from a fully stable-state distribution. These deviations reflect constraints imposed by tumor fitness selection pressures. The results point to CN changes that are more common in high-ploidy tumors and thus support altered selection pressures upon WGD.



中文翻译:

基因组不稳定和癌症中全基因组加倍的热力学能量学。

基因组不稳定性通过癌症驱动基因的扩增和缺失促进肿瘤发生。肿瘤集合的DNA拷贝数(CN)分析可以对每个肿瘤的概况进行热力学分析。发现CNs分布的自由能是平均染色体倍性的单调递增函数。这种依赖性在几种癌症类型中普遍存在。意外分析区分了两个主要的已知亚组:具有已经或未经历全基因组复制(WGD)的细胞的肿瘤。分析发现,具有较窄分布的CN状态在能量上对WGD过渡更有利。意外分析还确定了与完全稳态分布的偏差。这些偏差反映了肿瘤适应性选择压力所施加的约束。

更新日期:2020-08-05
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