‘Patchwork’ tumours prevalent across multiple cancer types

Breast cancer cells. Image credit: Wellcome Sanger Institute

‘Patchwork’ tumours prevalent across multiple cancer types

7 Apr 2021 - 15:22

Summary 

  • New research has found that nearly all tumours contain patches of different mutations showing that cancer cells continuously change over time
  • The study shows that, across cancer types, tumour cells acquire additional driver mutations even at the very latest stages of cancer evolution
  • Measuring genetic diversity within tumours will help to understand mechanisms for therapy resistance and relapse

07 April 2021, Cambridge – Researchers from the Pan-Cancer Analysis of Whole Genomes Consortium, which includes the Wellcome Sanger Institute, Francis Crick Institute and EMBL’s European Bioinformatics Institute (EMBL-EBI), characterised the origin and drivers of genetic mutations across multiple cancer types to help inform how these could impact cancer treatment.

When cancer cells divide, errors occur in the process of copying their DNA. These copying errors mean that different tumours can be made up of cells with a wide range of genetic diversity. This variation is a challenge because a treatment that works for one group of genetically related tumour cells — called a subclone — may not be effective against another. And certain subclones can initiate tumour spread or drug resistance.

In the study, published in Cell, researchers analysed the whole genomes of 2,658 cancer samples, spanning 38 types of cancer. They found that 95 per cent of samples contain at least one identifiable subclone, which is a patch of cells that show a large amount of genetic diversity and can therefore interfere with certain treatments. Understanding this genetic diversity could be used in the future to predict responses to treatments and enable personalised treatment plans based on the genetic makeup of the cancer.

Tumour evolution

The study confirms that, even at late stages of development, tumour evolution is driven by changes that benefit the cancer. The researchers show that the levels and types of genetic changes varied between cancer types and even in the same tumour, the genetic makeup of different subclones varied widely. These subclones are thought to arise due to particular evolutionary pressures present at different times during tumour development or affecting different areas of the tumour. For example, to resist a particular treatment or evade the immune system.

“This research has highlighted how pervasive these subclones are across different types of cancers and we have identified cancer type-specific patterns,” says Stefan Dentro, Postdoctoral Fellow at EMBL-EBI. “Being able to identify these patterns and the pressures that cause these mutations is crucial in understanding why cancers develop the way they do.”

Understanding genetic diversity

The team also found evidence that the evolution of subclones is affected by whether the genetic changes are helpful to the cancer or not. Subclones with advantages are more likely to develop. Research in this area has already shown that understanding this genetic diversity can be harnessed to predict survival or relapse, which could aid important treatment decisions.

“Cancers are constantly changing over time, so it’s important to recognise that a sample taken from a tumour reflects a single point in time and the cancer will continue to evolve after this,” says Peter Van Loo, Group Leader of the Cancer Genomics Laboratory at the Crick. “They can grow into a patchwork with sections driven by different mutations and evolutionary pressures. Understanding more about the evolution of subclones, why they develop in one direction over another, as well as how common they are, could help doctors better predict the levels of and types of variation likely to be present in a specific cancer type.”

This press release was originally published on the Wellcome Sanger Institute website

Source article

DENTRO, S., et al. (2021). Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Cell. Published online 07 04; DOI: 10.1016/j.cell.2021.03.009.

Funding

This research was funded by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and Wellcome.

Contact the news team

Vicky Hatch | Communications Officer

vhatch@ebi.ac.uk

Oana Stroe | Senior Communications Officer

stroe@ebi.ac.uk

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