Causes of cancer: Findings from the largest DNA analysis of the disease ever done

UK scientists have carried out a massive “archaeological dig” of cancer, analyzing the complete genome sequence of tumors from around 12,000 patients.

The team says the unprecedented amount of data allowed them to discover new patterns in cancer DNA – suggesting causes that are not yet understood.

They add that the “genetic clues” will help improve diagnosis and treatment. The research was published in the journal Science.

Cancer is a corrupted version of our healthy cells – mutations in our DNA change our cells until they grow and multiply out of control.

Traditionally, many cancers are categorized by doctors based on where they are located in the body and the type of cells involved — but whole genome sequencing can provide important new information, experts say.

‘Dinosaur footprints’

Whole genome sequencing is relatively new, but it is already available from the British public health system (NHS) for a small number of specific cancers, including some of the blood.

Lead researcher Serena Nik-Zainal, a consultant at Cambridge University Hospitals, explained to the BBC that the study is a kind of “archaeological dig” of people’s cancer.

“We can see patterns or imprints in the cancer field – like dinosaur footprints – of what’s going wrong. And each person’s cancer is different. Knowing that we can customize each person’s cancer report means we’re one step closer to customize treatment for them.”

Led by the University of Cambridge, the team of researchers analyzed anonymized DNA data provided by the 100,000 Genomes Project – an England-wide plan to sequence the entire genomes of patients affected by cancer and rare diseases.

With thousands of genetic changes observed in each tumor analyzed, the researchers were able to detect specific combinations of genetic alterations – so-called “mutational signatures” – that may be key to the development of cancers.

Comparing the data with other international projects, they confirmed some known patterns and discovered 58 new ones.

Some signatures may provide clues as to whether patients have had exposure to environmental causes of cancer — such as smoking.

Others provide more information about genetic abnormalities that may be amenable to specific drugs, the researchers say.

The researchers also created a computer program to help scientists and doctors verify that patients who have had the complete genome sequencing have any of the newly discovered mutational clues.

best treatment

Aubrey, a two-year-old girl from Bedfordshire, UK, was diagnosed with cancer when she was just 16 months old.

She did not participate in the study. But full genome sequencing has helped doctors identify the type of cancer she has — a rhabdomyosarcoma — a rare cancer that usually affects the muscles attached to bones. The results helped to choose the best possible treatment.

Anna, Aubrey’s mother, said: “Because of the unusual way in which Aubrey’s cancer came about, doctors were not sure of the exact type of cancer. Whole genome sequencing helped doctors know how to treat and maintain her. stable.”

“While we still have a challenging journey with Aubrey’s diagnosis and treatment, we are relieved to know that she does not have genetically inherited cancer and that we don’t need to worry that it could affect our other child or other family members as well.”

What is your genome?

• The genome is the information needed to build the human body and keep it healthy.
• It’s written in a “chemical language” called DNA
• The genome is made up of segments of DNA called genes.
• Most cancers are caused by cells with unusual genome changes.

Source: NHS England

Professor Matt Brown, Scientific Director of Genomics England, said: “Mutational signatures are an example of using the full potential of whole genome sequencing.

“We hope to use the mutational cues observed in this study and apply them back to our patient population, with the ultimate goal of improving the diagnosis and treatment of cancer patients.”