A comprehensive multi-cancer single-cell study by researchers at the University of Texas MD Anderson Cancer Center has found that tumours arise from a single ancestral cell and subsequently diversify through sudden bursts of chromosomal alteration rather than gradual genetic drift. The findings, published in Cancer Discovery, offer new insight into how genetic diversity within tumours contributes to treatment resistance and disease progression.
The research team analysed 94 tumours across seven cancer types, including bladder, breast, colorectal, glioblastoma, kidney, lung, and ovarian cancer, using single-cell sequencing on more than 62,000 aneuploid cells alongside whole-exome and RNA sequencing. This approach allowed the researchers to examine genetic variation at the individual cell level, addressing a limitation of conventional bulk sequencing methods, which average genetic signals across cells and can obscure clinically important subpopulations.
The analysis showed that tumour cells consistently share early-stage copy number alterations, confirming a common single-cell origin within each tumour. Frequently observed features, including TP53 mutations, genome doubling, and elevated copy number alteration burden, were associated with greater subclonal diversity, chromosome loss, and more aggressive disease behaviour.
To quantify how genetic changes accumulate over time, the researchers developed a Punctuated Evolution Index (PEI), which measures whether copy number gains occur as sudden, concentrated bursts or accumulate gradually. Tumours with high PEI scores acquired key genetic drivers rapidly and were associated with poorer clinical outcomes and more advanced disease stages. Tumours with greater genetic diversity were also more likely to form distinct spatial regions within the tumour mass.
The authors propose that these findings provide a foundational framework for larger-scale studies incorporating intratumoral diversity, to improve diagnostic precision and inform more personalised treatment strategies.
Source: Ye H et al. A pan-cancer single-cell analysis of intratumoral copy number diversity and evolution. Cancer Discovery (2026). DOI: 10.1158/2159-8290.cd-25-0964
