A comprehensive multi-cancer study from researchers at The University of Texas MD Anderson Cancer Centre has revealed that cancer cells within tumours are genetically diverse, yet all carry the same core genetic changes that can be traced back to a common ancestral cell, providing a single-cell view of how tumours adapt, survive and diversify.

Understanding this helps explain why some cancer cells manage to survive treatments, paving the way for more tailored diagnostic and therapeutic strategies.

The study, published in Cancer Discovery, was led by Nicholas Navin, Ph.D., chair of Systems Biology.

The research shows that cancer cells do not evolve slowly over time but, rather, grow through sudden bursts of rapid genetic changes that include copy number alterations (CNAs) – gains or losses of entire sections of DNA.

This creates a family tree of distinct new subpopulations that can influence tumour aggressiveness, metastasis and treatment response.

“Our findings provide the clearest views to date of how cancers originate and evolve at the single-cell level,” Navin said.

“By revealing both the shared early genetic events and the bursts that drive ongoing diversity, we now have a roadmap for developing smarter clinical diagnostic and treatment strategies to improve patient outcomes.”

How does understanding tumour evolution help patients?

Aneuploidy – when a cell contains an abnormal number of chromosomes – is a hallmark of tumours, but few studies have closely examined these genetic differences and how they evolve within tumours at a single-cell level.

Historically, cancer genomes have been analysed using bulk sequencing methods, which blend cells together and mask minor cell populations.

However, tumours are not uniform, and a single biopsy may miss important cell subpopulations, leading to potentially ineffective treatments.

Understanding this complexity helps guide better predictive diagnostic and treatment strategies that are more likely to work for patients with certain genomic features, such as high genetic diversity in genes that are used as biomarkers.

Single-cell sequencing allows researchers to answer the pressing question of how many cells in a normal organ give rise to cancer.

These findings could help lead to better prognostics by understanding which patients are more likely to have aggressive disease, metastasis, or therapeutic resistance based on the diversity of the cancer cells in their tumours.

How did the researchers investigate tumour diversity and what does it mean to have more genetic diversity?

The researchers analysed 94 tumours across seven cancer types (bladder, breast, colon, glioblastoma, kidney, lung, and ovarian) and used single-cell sequencing on over 62,000 aneuploid cells, along with whole-exome and RNA sequencing of patient samples.

They found that tumour cells share early-stage CNAs, meaning they have a common single ancestral origin starting from just one cell in the tissue.

Key features, such as TP53 mutations, genome doubling and elevated CNA burden, were frequent in many cancers and were linked to subclonal diversity, chromosome loss and more aggressive disease.

The researchers also found that tumours with higher genetic diversity were more likely to form distinct spatial regions within the tumour, allowing researchers to create a Punctuated Evolution Index (PEI) to quantify the evolutionary dynamics of CNAs.

PEI measures the degree to which these gains happen as a sudden punctuated burst at a given point in time or evolve gradually over time.

Tumours with high PEI tend to acquire key genetic drivers rapidly and were associated with poorer clinical outcomes and advanced stages of disease.

The researchers say these findings provide a foundational framework for future larger-scale investigations that account for intratumoural diversity, which can include more patients and other cancer types to better understand tumour evolution.

This, in turn, could lead to more accurate diagnosis and personalised treatment to improve clinical care and outcomes.

Article: A pan-cancer single-cell analysis of intratumoral copy number diversity and evolution

Source: University of Texas M. D. Anderson Cancer Center