5. februar 2020

Global study maps cancer mutations in large catalogue

Cancer mutations

Mutations in 38 different types of cancer have been mapped by means of whole genome analysis by an international team of researchers from, amongst others, the University of Copenhagen, Aarhus University, Aarhus University Hospital, and Rigshospitalet. The researchers have compiled a catalogue of the cancer mutations that will be available worldwide to doctors and researchers.

Image of Brain Cancer Chromosomes.
Brain cancer chromosomes. Photo: National Cancer Institute via Unsplash.

Globally, cancer is one of the biggest killers and in 2018, an estimated 9.6 million people died of the disease. In order to provide the best treatment for the disease, it is essential to find out which mutations are driving the cancer.

In a major international collaboration called Pan-Cancer Analysis of Whole Genomes (PCAWG), researchers from the University of Copenhagen, Aarhus University, Aarhus University Hospital and Rigshospitalet have helped to map mutations in 38 different types of cancer.

The mutations have all been combined into a sort of catalogue. The catalogue, which is already available online, allows doctors and researchers from all over the world to look things up, consult with and find information about the cancer of a given patient.

‘Most previous major studies have focused on the protein coding two percent of the genome. We have studied and analysed the whole genome, and our analyses of mutations that are affecting cancer genes have enabled us to genetically explain 95 percent of the cancer occurrences we have studied by means of mutations,’ says co-author Joachim Weischenfeldt, Associate Professor at the Biotech Research & Innovation Centre, University of Copenhagen, and the Finsen Laboratory, Rigshospitalet.

‘So, if you know which mutations have caused cancer, the so-called driver mutations, you will be able to better tailor a treatment with the most suitable drugs or design new drugs against the cancer. Precision medicine is completely dependent on the mapping of driver mutations in each cancer, in relation to diagnosis, prognosis and improved treatment,’ says co-author Jakob Skou Pedersen, professor at Bioinformatics Research Centre and Department of Clinical Medicine, Aarhus University, and Aarhus University Hospital.

The new research results are published in a special edition of the scientific journal Nature with focus on PCAWG. To date, it is the largest whole genome study of primary cancer. This means that the analysis was performed based on material from the tissue in which the tumour originated and before the patient has received any treatment.

From a Handful to 100,000 Mutations

The researchers have mainly analysed and had data on the most common types of cancer such as liver, breast, pancreas and prostate cancer. In total, they have analysed whole genome-sequenced tumour samples from more than 2,600 patients.

Based on their analyses, they could see that the number of mutations in a cancer type varies a lot. Myeloid dysplasia and cancer in children have very few mutations, while there may be up to 100,000 mutations in lung cancer.

The infographic is an overview of the different cancer types studied in the Pan-Cancer Project. The lower part also lists the six cancer types (for men and women) for which the most samples were available. Credit: Rayne Zaayman-Gallant/EMBL. Click on the graphic below to enlarge it.

Infographic showing studied cancer types.

But even though the number of mutations spans widely, researchers could see that on average there were always 4-5 mutations that were driving the disease, the so-called drivers – no matter what type of cancer it was.

‘It is quite surprising that almost all of them have the same number of driver mutations. However, it is consistent with theories that a cancerous tumour needs to change a certain number of mechanisms in the cell before things start to go wrong,’ says Jakob Skou Pedersen.

In the catalogue, the researchers have divided the mutations into drivers and passengers. Driver mutations provide a growth benefit for the cancer, while passenger mutations cover all the others and are harmless. The vast majority of all mutations are passengers.

Genetics or Tissue

To store and process the vast amount of data, the research team has used so-called cloud computing, using 13 data centres spread across three continents. They have had centres in Europe, the US, and Asia.

The large data set has been necessary to establish what was common and unique to the different types of cancer. Today, cancer is divided according to the tissue in which the disease originates, for example breast, brain, and prostate.

The researchers found many things that were completely unique to each type of tissue. Conversely, they also found many common traits across the tissue types. According to Joachim Weischenfeldt, there is thus a need to rethink the way we think about cancer.

‘Cancer is a genetic disease, and the type of mutations is often more important than where the cancer originates in the body. This means that we need to think of cancer not just as a tissue-specific disease, but rather look at it based on genetics and the mutations it has.’

‘For example, we may have a type of breast cancer and prostate cancer where the driver mutations are similar. This means that the patient with prostate cancer may benefit from the same treatment as the one you would give the breast cancer patient, because the two types share an important driver mutation,’ says Joachim Weischenfeldt.

The International Cancer Genome Research Consortium has been supported by national foundations, including Independent Research Fund Denmark.

Read the special edition of Nature, where most of the PCAWG Consortium's results have been collected and published. The main article "Pan-cancer analysis of whole genomes" can be read here. "Patterns of somatic structural variation in human cancer genomes" can be read here and "Analyses of non-coding somatic drivers in 2,658 cancer whole genomes" can be read here. Read more about the PCAWG Consortium here.


Head of Group and Associate Professor Joachim Weischenfeldt, +45 60573080, joachim.weischenfeldt@bric.ku.dk

Professor Jakob Skou Pedersen, +45 31418132, jakob.skou@clin.au.dk

Press Officer Cecilie Krabbe, +45 93565911, cecilie.krabbe@sund.ku.dk