The team of Han Zeguang and Su Xianbin of Shanghai Jiaotong University proposed a new strategy for predicting tumor clonal structure

Recently, Ann NY Acad Sci, a classic academic journal with nearly 200 years of publishing history, published a paper
entitled "Accurate tumor clonal structures require single-cell analysis" by Han Zeguang, Su Xianbin, and colleagues of the Institute of Systems Biomedical Sciences of Shanghai Jiao Tong University 。 This study systematically compares the similarities and differences of single-cell and population-level tumor clonal structures for the first time, and finds that coexisting tumor subclonals and dynamic evolution may be hidden under the appearance of neutral evolution, shaking the traditional paradigm of tumor clonal structure prediction based on population-level mutations
.

It is generally believed that tumors originate from single-cell mutations, and then as cells divide, there will be subclonal populations of tumors with different combinations of mutations, and their evolution is closely related to
clinical treatment, metastasis, and recurrence.

Using the early obtained single-cell, single-mutation level of human liver cancer clonal evolution data (J Hematol Oncol, 2021, 14:22, see https://scsb.

In order to explore the universality of this discovery in tumor evolution, the team further compared the population level of colorectal cancer samples and single-cell exon data analysis, and also found that in the case of missing subclonal mutation peaks at the population level, single-cell mutations not only revealed multiple coexisting tumor subclones, but also reconstructed the dynamic evolutionary history
of these subclones.

The study suggests that the VAF ranges of different co-mutant groups overlap, making it difficult to match mutations to specific tumor subclones based on population-level VAF values, which directly shakes the theoretical basis of
current tumor clone structure prediction.

Su Xianbin, associate researcher of the Institute of Systems Biomedicine, Bai Shihao, a doctoral candidate of the class of 2019, Professor Xie Ganggang of Nantong University and Shi Yi, associate researcher of Bio-X Research Institute, were the co-first authors of the paper, and Han Zeguang, Su Xianbin, and Long Qi, the research group leader of Guangzhou Medical University, were the co-corresponding authors
of the paper.

Paper link: https://doi.