Most Comprehensive Analysis of Cancer Genomes to Date

17 Mars, 2020, 07:41 | Auteur: Therese Cote
  • The Pan Cancer Project brought together over 1,300 researchers globally to tackle the mammoth task of sequencing the genomes of 38 types of cancer in nearly 2,800 patients. — Reuters pic

For anyone finding themselves on an unknown street these days, directions are just a few taps away on a mobile phone map.

Researchers have submitted human cancer samples from all over the world to produce the Global Cancer Atlas.

The hallmark of a cancer cell is its unregulated growth.

A cancer is a corrupted version of our own healthy cells - mutations to our DNA change our cells until eventually they grow and divide uncontrollably. The cancers range from common ones like colorectal and breast cancers to rare cancer types including pancreatic and brain cancers.

The analysis is published in Nature as part of a wider collection of 22 papers from the Pan-Cancer project.

Previous published studies-such as those from the USA -funded Cancer Genome Atlas (TCGA)-originally looked only at the "exome", protein-coding DNA that make up just 1% of the genome, of tumors because it was cheaper and easier. The researchers then modelled how different types of cancer develop over time.

Cancer is often said to be many diseases, rather than one disease, because of the vastly different way that different kinds of cancers are known to behave.

Previously, focus had been on the genes that code for proteins, but this only accounts for around one percent of the genome. "This process is fueled by mutations in the cells' genomes", said co-lead author Moritz Gerstung, PhD, group leader at European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI), in the statement. "For more than 30 cancers, we now know what specific genetic changes are likely to happen, and when these are likely to take place".

In working with these data and sharing them as a resource for scientists, researchers involved in the Pan-Cancer project were conscientious about the privacy of the patients who had donated their samples. This is primarily the result of improved methods for analysing the DNA sequence data, compared with the state of the art in 2013.

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"We are finding that cancer represents the far end of an enormous spectrum of change", said Campbell. "The combination of genetic scars responsible for each cancer type is complex and involves dozens of different genes for each cancer type", Professor Grimmond says.

The work significantly improves our fundamental understanding of cancer and signposts new directions for its diagnosis and treatment, the researchers report.

Through a new method of "carbon dating," Pan-Cancer researchers discovered that it is possible to identify mutations which occurred years, sometimes even decades, before the tumour appears.

Experts stressed early mutations that led to the development of some types of cancer occur mostly in nine genes, and the discovery may facilitate a possible treatment. This showed where DNA mutations arose, and whether they had been copied and duplicated as more DNA changes accumulated. Each of these mutations leaves a "genetic fingerprint", referred to as a mutational signature. Sequencing a cancer genome is still expensive, though the cost is falling, says Campbell. For example, across cancer types, deletion of TP53 is one of the most frequent initiating mutations, including in ovarian cancer. This uniqueness is a huge advantage when a patient presents with a cancer that has moved or metastasized.

Identifying the earliest mutational events for any cancer would be an invaluable step toward relevant treatment intervention.

This unprecedented level of data crowd-sourcing means researchers, clinicians and industry can now work together, anywhere across the globe. Campbell and Stein said they hope it will be used to generate new detection and treatment strategies.

There is one driver mutation in about 95 percent of all tumor samples than just 67 percent with exome sequencing, showing that more cancer patients can be matched to medicine or treatment that targets the particular protein made by the driver gene.

"Although the genome of each patient's cancer is unique, there are a finite set of recurring patterns of genetic damage, so with large enough studies we can identify all of them", Professor Grimmond says. "With the knowledge we have gained about the origins and evolution of tumours, we can develop new tools to detect cancer earlier, develop more targeted therapies and treat patients more successfully".



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