Cancer is a disease of the genome. Each cell within our body contains all of the genetic code required for human life and development. This genetic code is composed of over three billion DNA molecules, joined together into 46 long strings known as ‘chromosomes’. Collectively, the DNA that makes up all 46 chromosomes is known as the ‘genome’.
Every time a cell divides, it makes two copies of its DNA that are passed on to its daughter cells, but occasionally errors are made during copying the DNA, resulting in mutations in the daughter cells. The great majority of mutations are harmless, but some mutations can give a cell an advantage that enables it to out-compete the other cells around it, and develop into a tumour.
Cancer genomics is the study of these mutations. It encompasses a broad scientific field including discovering the environmental factors that cause the mutations (aetiology), the molecular mechanisms by which they are caused (molecular biology) and those mutations most likely to cause cancer (genetics).
Cancer Genomics in Manchester
Manchester is home to The Manchester Centre for Genomic Medicine, one of the leading centres for clinical genomics in Europe and home to 250 doctors, genetic counsellors, informaticians, scientists and other research staff. Cancer genetics and neurofibromatosis are two of the research themes within this Centre with scientists investigating how to personalise treatment, understand gene changes and predict response to treatments.
Additionally, our scientists are playing a leading role in the 100,000 Genomes Project, which has sequenced the whole genomes of 70,000 patients with rare genetic diseases as well as the genomes of 15,000 cancer patients, with a particular focus on lung, colorectal, womb, and ovarian cancers.
As members of the Pan Prostate Cancer Group, an international consortium that has sequenced the whole genomes of over 1200 prostate cancers, Manchester researchers have made numerous discoveries that change how we view prostate cancer. These include the discovery of 22 genes that are likely to cause prostate cancer if mutated, the observation of mutations in normal prostate tissue that may be indicative of the origins of prostate cancer, and the identification of the genomes of the cells that are responsible for the metastatic spread of prostate cancer.
Through leading the analysis of Evolution and Heterogeneity within the Pan Cancer Analysis of Whole Genomes project, the largest published study of cancer whole genomes to date, Manchester scientists discovered that key genomic aberrations can occur several years, or even decades, prior to diagnosis, raising the possibility of earlier detection. In addition, it was found that the mutational processes that cause mutations often change over time, with differences between the time of initial formation of a tumour and later times, at which we often observe substantial genomic heterogeneity.
Specialist cancer genomics researchers in Manchester aim to bring the benefits of genomic medicine to a wider spectrum of people. One way of achieving this is to collaborate with cancer researchers in less economically developed parts of the world. One example is a project studying the genomics of breast cancer in Nigeria in collaboration with Funmi Olopade, an expert in breast cancer based at the University of Chicago, and also collaborate with cancer researchers and clinicians based in Kenya and South Africa.
Working with the Digital Services team at The Christie, researchers are drawing together multiple types of medical data, including electronic health records and genomic test data. In addition, using machine learning approaches, the team aim to use the power of big data to improve prognosis of cancer.
The great majority of cancer deaths result from metastatic tumours. By studying the genomics of metastatic cancers arising from primary tumours in different organs, researchers aim to identify the tumours that are most likely to metastasise before they spread. This will enable doctors to personalise the treatment of cancer patients at an earlier stage.
Through the Cancer Research UK RadNet Manchester Radiation Research Unit, Manchester researchers are using genomics to identify patients that are most likely to benefit from radiation therapy, as well as those that may respond better to other treatments such as surgery.