The analysis of thousands of tumors revealed a treasure trove of evidence of the causes of cancer, which is a significant step towards personalizing treatment.
Researchers say that for the first time, it is possible to find patterns – called mutation signatures – in cancer DNA.
They provide clues, including whether the patient has had previous exposure to environmental causes of cancer, such as smoking or UV light.
This is important because these signatures allow doctors to examine each patient’s tumor and compare it to specific treatments and medications.
However, these models can only be detected by analyzing the vast amounts of data found by sequencing the entire genome – identifying the genetic makeup of the cell.
The study’s lead author, Serena Nick-Zainal, is a professor of genomic medicine and bioinformatics at the University of Cambridge and an honorary consultant in clinical genetics at Cambridge University hospitals.
She said: “It’s like watching a very busy beach with thousands of footprints in the sand. To the untrained eye, the prints seem random and meaningless.
But if you are able to study them closely, you can learn a lot about what is happening, to distinguish between animal and human footprints, whether an adult or a child, in which direction they travel, etc.
“It’s the same with mutation signatures.
The use of whole genome sequencing can identify which “imprints” are appropriate / important and reveal what happened through the development of cancer.
The researchers analyzed the complete genetic makeup or whole genomic sequences (WGS) of more than 12,000 NHS cancer patients.
They were able to spot 58 new mutation signatures, suggesting that there are additional causes of the cancer that have not yet been fully elucidated.
Nick-Zainal said: “The reason it’s important to identify mutational signatures is because they’re like fingerprints at a crime scene – they help identify those responsible for cancer.
“Some mutational signatures have clinical or therapeutic consequences – they may highlight abnormalities that may be targeted by specific drugs or may indicate a potential ‘Achilles’ heel’ in certain cancers.”
Dr Andrea Degasperi, a research fellow at the University of Cambridge and a first author, said: “Sequencing the entire genome gives us a complete picture of all the mutations that have contributed to each person’s cancer.
“With thousands of cancer mutations, we have the unprecedented power to look for commonalities and differences between NHS patients, and in this way we have uncovered 58 new mutational signatures and expanded our knowledge of cancer.”
The findings are included in the NHS, as researchers and clinicians are already using a digital tool called FitMS that will help them identify the mutation signature and potentially inform cancer management more effectively.
This study was supported by Cancer Research UK and published in the journal Science.
Genomic data was provided by the 100,000 Genomes Project, a clinical research program in England for sequencing 100,000 whole genomes from around 85,000 patients affected by a rare disease or cancer.
Michelle Mitchell, CEO of Cancer Research UK, said: “This study shows how powerful whole-genome sequencing tests can be to provide clues as to how cancer may have developed, how it will behave and what the possibilities are. for treatment would work best.
Prof. Matthew Brown, Chief Research Officer of Genomics England, said: “Mutational signatures are an example of exploiting the full potential of WGS.
“We hope to use the mutational evidence observed in this study and apply it back to our patient population, with the ultimate goal of improving the diagnosis and management of cancer patients.
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