Update to COSMIC drives precision oncology

The Cancer Mutation Census combines biological, biochemical and population data to enable users to understand which DNA mutations drive human cancers

The Catalogue of Somatic Mutations in Cancer (COSMIC), based at the Sanger Institute, has launched a new feature to predict the impact of all the mutations that have been seen in human cancers. The ‘Cancer Mutation Census’ integrates biological, biochemical and population information from multiple sources, allowing users to discover and understand the important mutations that are driving different types of cancer. This is aimed at improving the application of precision oncology, where a patient’s tumour genetics are used to determine their treatments. The Cancer Mutation Census (CMC) is available at https://cancer.sanger.ac.uk/cmc/home

COSMIC is the world’s most comprehensive knowledge centre for cancer mutations. Manually curated by a team of experts at the Wellcome Sanger Institute, it includes data from more than 22 million somatic mutations across the genome, spanning 1,460 types of cancer. It integrates data on multiple different types of mutation seen in cancer genes and genomes, as well as data on gene expression, gene function and 3D protein structure. Users can view or download the data in multiple ways.

Developed with support from AstraZeneca, the aim of COSMIC’s new system is to help users understand which mutations are likely to be causing cancer, and which are only a result of the disease. Uniquely, the Cancer Mutation Census doesn’t rely solely on AI and Machine Learning algorithms to score mutations. Experts curate the database and calculate biological properties, bringing together multiple different perspectives on what constitutes a driver mutation.

All the data in the CMC is downloadable, so its interpretations are fully transparent, and it is clear why a mutation is classified with either high or low impact. Users are able to see the biological reasoning and the evidence base used.

The work is part of a push for COSMIC to further support precision oncology. By early 2021 new system describing the ‘actionability’ of cancer mutations will be published. Aimed at scientists developing new genomic medicines, this will allow users to see which mutations can be targeted with a wide range of treatments in the clinic.

“The challenge for precision oncology is determining which mutations matter among the tens of thousands present in any single cancer genome. This new feature brings together the comprehensive resources of COSMIC with the biological features which define driver mutations. That speeds up massively what people can do with the resource – whether they are designing new diagnostics or therapeutics, or undertaking research to understand cancer development and biology.”

Dr Zbyslaw Sondka, Senior Staff Scientist at COSMIC, based at the Wellcome Sanger Institute

This initial release of the CMC includes metrics such as ClinVar significance, dN/dS ratios, and variant frequencies in normal populations (gnomAD). These are all integrated alongside observations from the huge COSMIC database on mutation prevalence.

The update is included as standard for all licence holders, and free for users at academic and non-profit organisations.

“COSMIC brings together all the world’s information on the mutations driving every form of human cancer. We’re now building a pipeline to characterise the enormous range of mutations driving so many different forms of human cancer, and describe in detail those that are meaningfully actionable in the real world. COSMIC’s growing range of resources gives us the most comprehensive insight to support global precision oncology.”

Dr Simon Forbes, Director of COSMIC at the Wellcome Sanger Institute

More information

Funding:

COSMIC license income, AstraZeneca