Cancer, Ageing and Somatic Mutation

Our Approach


The Cancer, Ageing and Somatic Mutation Programme seeks to provide leadership in data aggregation and informatics innovation, developing high-throughput cellular models of cancer for genome-wide functional screens and drug testing, and exploring basic scientific questions about the role somatic mutation plays in clonal evolution, ageing and development.

The Cancer, Ageing and Somatic Mutation Programme will:

  • conduct computational meta-analyses on large, aggregated cancer genome data sets to identify the long tail of infrequently mutated cancer genes, to characterise mutational signatures and to inform on the evolution of cancer cell clones.
  • take a lead in developing the next generation of cancer cell lines and use cell lines to systematically explore in vitro sensitivity to large numbers of anticancer drugs and drug combinations in order to inform choice of cancer types for early drug trials.
  • continue to develop and maintain the COSMIC database of somatic mutations.
  • use CRISPR-Cas technology to carry out genome-wide screens of gene-gene, gene-drug and cancer-microenvironment interactions in cells and mice in order to explore fundamental biology and to identify drug targets and drug resistance/sensitisation mechanisms.
  • seek to identify the mutational processes underlying mutational signatures found in cancers, characterise the mutational processes operating in normal cells, use phylogenetic analyses of somatic mutations in humans to explore cellular lineages during embryonic development
  • explore mutation accumulation during ageing and characterise its consequences for development of neoplastic clonal expansions in non-cancerous cell populations throughout life.

Our Work




Sanger Institute, Genome Research Limited


Oesophageal cancer organoid

The Cancer, Ageing and Somatic Mutation Programme encompasses three Projects that respectively cover the genomics of human cancers; functional analysis of the cancer genome using a range of in vitro and in vivo model systems; and the characterisation of somatic mutations in development and adult homeostasis in health and disease.

A key challenge in cancer genomics is of heterogeneity. We see extensive variability in genomes among tumours of different tissue types, among different patients within a tissue type and among subclones within a given patient’s cancer. The rejoinder to the challenge of heterogeneity is scale.

For discovery of new cancer genes and mutational processes, aggregation of tens of thousands of cancer genomes is needed – we are establishing a virtual marketplace for exchange of genomes and informatics and develop increased functionality through the COSMIC portal.

For understanding the biology of gene-gene, gene-drug and gene-microenvironment interactions, a considerably broader range of in vitro and in vivo model systems is required – we are generating 1,000 organoid cultures from human cancers, characterising their genomes, functional dependencies and drug response, and we are expanding our in vivo models to study the interface between cancer and the immune system and microenvironment.

For setting cancer in the context of ageing tissue, study of normal adult homeostasis is important – we are studying mutational processes, clonal dynamics and cellular competition in thousands of non-cancerous cells and samples from a range of tissue types, in health and disease.

We are developing the concept of using somatic mutations present at adulthood to reconstruct the phylogeny of an individual’s development. The depth of insight is limited only by the numbers of cells sequenced and cheaper sequencing will enable us to see far back to the early stages of life, and study inter-individual variation in development. We also seek similar scaling up of the in vitro experiments, sampling deeper into the landscape of cancer genes, gene-gene interactions and combination drug responses.

We work closely with the Human Genetics and Cellular Genetics programmes.

Research

Groups

Recent Findings