A massive genomic study reveals some causes of cancer

For a long time, cancer was identified and treated according to its location (lung, breast, brain, etc.). Since the acceleration of genetic sequencing, medicine has begun to look at the disease from another angle: that of the type of mutations found in tumors. A way to better understand how they appear and how to treat them. The great advances in this field have just been published by the University of Cambridge in the journal Science. By analyzing patients’ tumors, the team was able to identify several factors that lead to the disease.

To do this, the researchers relied on the 100,000 Genomes Project, a large clinical study launched in England that aimed to sequence 100,000 whole genomes, from 85,000 patients affected by cancer or rare diseases. In all, the Cambridge team was able to work on 12,000 cancer patients whose genomes had been completely sequenced.

The genome of cancer cells often has many genetic mutations. However, the sequencing technique allows for a better understanding and analysis of these mutations in order to identify which combinations of mutations can cause specific cancers. A kind of similar pattern that comes up again and again, these “genetic signatures“It allows us to visualize which mutation processes led to the development of the tumor.”This gives us a picture of all the mutations that have contributed to the development of cancer in an individual. With thousands of cancer mutations, we have the unprecedented power to look at the similarities and differences in these patients.“, explains Dr. Andrea Degasperi, from the oncology department at Cambridge University Hospital, the first author of the study.

A palette of 120 reference signatures

Mutations identified in lung cancer when caused by cigarette smoke. Around the circumference of the circle, the numbers X and Y designate the chromosomes in which the mutations have been observed. Photo credit: Serena Nik-Zainal, Cambridge University

The results confirmed many “mutational signatures“, which had already been identified in the past but also to identify much rarer signatures. In trying to find similarities between the results obtained, scientists were able to identify specific signatures according to the patient’s exposure to environmental causes of cancer, such as tobacco or UV exposure.

These signatures also made it possible to identify the causes of cellular dysfunction. In addition, 58 mutational signatures have been identified, the causes of which are not yet known, although they are not yet fully understood. The authors have shown that for each tumor there are a limited number of these specific signatures. In total, 120 reference signatures could be identified. A very full palette that, however, leaves room for less frequent configurations: certain signatures, much rarer, are not frequently found in the population.

At the dawn of a new era of treatments

From this research, the health data of the patients allowed to see all the tumors of a population from another angle. “Participation of the National Health Service (NHS, British healthcare system, editor’s note) shows how data can transform the care we provide to patients“Professor Dame Sue Hill, head of the NHS genomics department, described the genomics as”cornerstoneBased on their results, the researchers developed an algorithm called Signaure Fit Multi-Step (FitMS), capable of searching for signatures on new samples of cells extracted from tumors.

First, the program detects frequent, organ-specific signatures. Second, the algorithm is able to tell if there are other rarer signatures in the tumor DNA as well. One truly “crime scene with fingerprints“According to Serena Nik-Zainal of the Department of Oncology at Cambridge University Hospital. These results are a goldmine for imagining new treatments that can accurately target these mutational weaknesses.”Some of the signatures have clinical implications and may lead to the development of treatments. They show certain abnormal characteristics that can be addressed with specific drugs“, explains Dr. Andrea Degasperi. A hope for, in the long term, an innovative treatment for all types of cancer.

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