New DNA Sequencing Tool Reveals Hidden Mutations and Early Cancer Growth

Researchers have refined a powerful DNA sequencing tool that can uncover hidden mutations that occur naturally in our bodies as we age.In the largest study to date, they have used the tool to provide insights into the earliest steps of cancer development and the role of mutations in healthy tissue.

The new study, published today (8 October) in Nature, was led by researchers from the Wellcome Sanger Institute, in collaboration with the TwinsUK study at king’s College London. The researchers introduce an improved version of nanorate sequencing (NanoSeq) – an ultra-accurate DNA sequencing technique.

By applying targeted NanoSeq to cheek swabs and blood samples from more than 1,000 volunteers, the team uncovered a rich landscape of mutations in healthy tissues, giving the most detailed picture so far of how tissues mutate over time.

As people age, their cells naturally acquire DNA mutations, known as somatic mutations. Most are harmless, but some can provide a growth advantage, leading to ‘clones’ of cells that carry the same mutations. As they multiply, some patches of clones have the potential to become the earliest stage in cancer development, but they may also contribute to aging and other diseases.

Detecting mutations in tumors is straightforward, but historically, locating rarer mutations in normal tissues has been extremely challenging. This is because most sequencing methods do not have the accuracy to distinguish real mutations from errors in biopsies composed of thousands of clones, like most non-invasive biopsies.

To overcome this, researchers from the Sanger Institute and their collaborators refined NanoSeq, so that it can precisely measure mutation rates, identify mutation patterns, and detect key driver mutations in any tissue.

In this new study, for the first time, the researchers used targeted NanoSeq to analyze non-invasive human samples – cheek swabs – from 1,042 participants in the TwinsUK cohort, alongside 371 blood samples. the volunteers ranged in age from 21 to 91, and included smokers and non-smokers, people with different histories of alcohol consumption, and varied lifestyles and exposures to cancer.

The researchers discovered over 340,000 mutations in cheek cells, including over 62,000 in genes known to drive