A COSMIC catalogue of cancer data, with Mutographs' Ellie Dunstone

13 July 2021
Ellie Dunstone headshot

Earlier this year, COSMIC - the world's largest and most comprehensive resource for exploring somatic mutations in cancer - celebrated the curation of its 10 millionth mutation. 

PhD student Ellie Dunstone discusses how COSMIC supports the Mutographs team, providing access to a huge breadth and depth of quality, curated data. 

Scientists have thought that cancer is linked to changes in the DNA since the late 19th century, when the German pathologist David von Hansemann noticed that the abnormal division of cancer cells under the microscope led to errors in the number of chromosomes. But it was only in 1982 that the first naturally occurring mutation linked to human cancer was discovered.

This mutation, changing a single DNA letter in the HRAS gene, paved the way for the identification of many more mutations that transform normal genes into drivers of tumour development. As more genes and mutations linked to cancer were discovered, scientists needed a way to collect and share this information.

They needed to build a catalogue of genetic changes in cancer.

COSMIC, the Catalogue Of Somatic Mutations In Cancer

COSMIC is a comprehensive resource used to record and investigate the genetic mutations found in cancer. Launched in 2004, the database originally covered only four genes: HRAS, KRAS, NRAS and BRAF. These genes are all in the same molecular pathway responsible for regulating cell division. A mutation in one of these genes can lead to errors in this process, leaving a cell dividing uncontrollably and causing the growth of a tumour.

Recent leaps forward in large-scale genetic sequencing of tumours has led to the discovery of hundreds of genes linked to cancer. COSMIC has had to grow in size to match the huge amount of data being generated – and has now catalogued over 70 million mutations from dozens of different cancer types. Through a range of resources, the COSMIC team expertly curates a range of information about mutations in cancer, including the Cancer Gene Censusa list of the most important genes involved in driving cancer, and COSMIC-3Da platform for understanding how mutations affect the 3D structure of the proteins produced by genes linked to cancer.

These resources are used by scientists worldwide for projects relating to cancer biology and drug discovery, with over 5,000 page views every day.

How does COSMIC support the Mutographs project?

COSMIC also curates a list of patterns of mutation, called mutational signatures, caused by a range of different things, from errors in cell division to damage from external forces like ultraviolet light. Looking for these signatures in patients’ tumours can help scientists to identify the causes of cancer. One example is the story of aristolochic acida chemical found in a number of traditional medicines and that was already known to be linked to kidney problems. But the discovery of its specific mutational signature in patients with liver cancer in Asia led scientists to link the use of some kinds of herbal remedies to this disease.

Discoveries like this can aid public health initiatives to help people limit their exposure to dangerous substances, reducing their cancer risk. The Mutographs team uses COSMIC’s list of mutational signatures to help identify possible causes of patients’ cancers and understand how this varies in different parts of the world.

From mutations to medicines

By keeping track of the mutations that cause cancer, COSMIC can also aid the development of targeted cancer treatments and work out whether an existing treatment might work for other cancer types. For example, the discovery that melanoma is often driven by a mutation in the BRAF gene led to the development of targeted drugs, dramatically improving outcomes for some people with cancer. The same BRAF mutation has since been found in some colon cancer patients. Scientists are now researching how the targeted melanoma drugs might also be added to colon cancer treatment regimens to make them more effective.

One of the newest COSMIC projects, Actionability, aims to track the availability of drugs that target specific mutations in cancer and monitor related clinical trials. This resource will support research into targeted cancer treatments, with the ultimate aim of using our increasing knowledge of genetic changes in cancer to improve personalised treatments. So far, full information has been collected for 39 genes, with a further 161 annotated with some human clinical study data.

As more and more data is generated, COSMIC continues to grow and gather important information. This information will be of huge value to the Mutographs team, who will continue to use COSMIC resources in their search for finding preventable causes of cancer. Very soon, COSMIC will be launching more exciting products that will help provide further answers to some of the key questions in global cancer research.

The COSMIC team is part of the Wellcome Sanger Institute, based at the Wellcome Genome Campus, Cambridge, UK. 

Discover more about our Mutographs team.