Accurate tumor clonal structures require single-cell analysis,Annals of the New York Academy of Sciences

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Accurate tumor clonal structures require single-cell analysis
Annals of the New York Academy of Sciences ( IF 4.1 ) Pub Date : 2022-09-08 , DOI: 10.1111/nyas.14897
Xianbin Su ₁ , Shihao Bai ₁ , Gangcai Xie ₂ , Yi Shi ₃ , Linan Zhao ₁ , Guoliang Yang ₄ , Futong Tian ₅ , Kun-Yan He ₁ , Lan Wang ₁ , Xiaolin Li ₁ , Qi Long ₆ , Ze-Guang Han ₁

Affiliation

Tumor clonal structure is closely related to future progression, which has been mainly investigated as mutation abundance clustering in bulk samples. With relatively limited studies at single-cell resolution, a systematic comparison of the two approaches is still lacking. Here, using bulk and single-cell mutational data from the liver and colorectal cancers, we checked whether co-mutations determined by single-cell analysis had corresponding bulk variant allele frequency (VAF) peaks. While bulk analysis suggested the absence of subclonal peaks and, possibly, neutral evolution in some cases, the single-cell analysis identified coexisting subclones. The overlaps of bulk VAF ranges for co-mutations from different subclones made it difficult to separate them. Complex subclonal structures and dynamic evolution could be hidden under the seemingly clonal neutral pattern at the bulk level, suggesting single-cell analysis is necessary to avoid underestimation of tumor heterogeneity.

中文翻译：

准确的肿瘤克隆结构需要单细胞分析

肿瘤克隆结构与未来进展密切相关，主要研究为大量样本中的突变丰度聚类。由于单细胞分辨率的研究相对有限，仍然缺乏对这两种方法的系统比较。在这里，我们使用来自肝癌和结直肠癌的大量和单细胞突变数据，检查单细胞分析确定的共突变是否具有相应的大量变异等位基因频率 (VAF) 峰。虽然批量分析表明不存在亚克隆峰，并且在某些情况下可能存在中性进化，但单细胞分析确定了共存的亚克隆。来自不同亚克隆的共突变的大量 VAF 范围重叠使得难以将它们分开。

更新日期：2022-09-08

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