Global Cancer Genomics

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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 the 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 1,200 prostate cancers, Manchester researchers have made numerous discoveries that have changed 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 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. We have also recently discovered that prostate cancers may be divided into two 2 types, based on how they arise from healthy cells and progress with time, which we call ‘evotypes’.

Global Cancer Genomics

Ethnicity affects both the prevalence and aggressiveness of many types of cancer. For example, Black men are twice as likely to get prostate cancer than White men, and Black women are more likely to develop the most aggressive type of breast cancer than White women.

Despite this, most cancer research to date has been carried out in developed countries, with high income to invest in cancer research, and with patient cohorts primarily of European origin. To study the effects of ethnicity and the environment on cancer formation and progression, we must take a global perspective and collaborate with cancer researchers from across Africa and Asia.

Future Interests

How does genetic ancestry interact with environmental factors to cause aggressive cancers?
How are cancers different at a molecular level in different countries?
What types of treatments are more likely to be effective against cancers in low and middle income countries?

Manchester Cancer Research Centre - Global Cancer Genomics

Breast cancer in Nigeria

Since 2016, Professor David Wedge has worked with Professor Olufunmilayo Olopade (University of Chicago) to study the genomics of breast cancer in Nigeria. They have found that a gene called GATA3 is more likely to be mutated in breast cancer in Black Nigerian women than in White women in the USA.

Furthermore, mutations in GATA3 and another cancer driver gene called TP53 define two different subtypes of breast cancer. People with breast cancers carrying GATA3 mutations are diagnosed on average ten years earlier than those carrying TP53 mutations.

Prostate cancer in Africa

Professor Vanessa Hayes (University of Sydney, University of Pretoria and The University of Manchester), in collaboration with researchers including Professor David Wedge, have studied prostate cancer in South Africa.

They have found that prostate cancers in Black men in South Africa have a higher mutation rate than White men in Australia. The mutations are likely to occur in a different set of genes and define a previously unknown subtype of prostate cancer. Through the ongoing HEROIC study, they are now looking at environmental effects on prostate cancer in South Africa, Kenya, Namibia and Nigeria.

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Oesophageal squamous cell cancer in Kenya

Professor Rob Bristow is leading a research study in collaboration with Professor George Njoroge (Kenyatta University Teaching Research and Referral Hospital, Nairobi) to explore the likely causes of a common type of throat cancer, called oesophageal squamous cell cancer (OSCC), in Kenya.

Whilst the most common type of throat cancer in the UK is oesophageal adenocarcinoma, in Kenya and most low and middle income countries, the most common type of throat cancer is oesophageal squamous cell cancer. The research team hope to find out the reasons for this, through improving early detection of OSCC and analysing the patterns of genetic mutations that occur in these cancers.

Breast cancer in Hong Kong and Malaysia

Dr Avraam Tapinos and Dr Aliah Hawari, both researchers within Professor David Wedge’s research group, are researching the genomics of breast cancer in both Hong Kong and Malaysia. They are particularly interested in the interaction between breast cancer cells and the surrounding healthy cells; and in the cellular processes that lead to mutations and copy number aberrations in breast cancer, such as homologous repair defects (HRD).

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CASE STUDY: Breast cancer in Black African women with Professor David Wedge.

In this episode of our One in Two podcast, we speak to David Wedge, Professor of Cancer Genomics and Data Science, about how analysing genomics can improve our understanding of the aggressiveness of breast cancer.