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The changing genome: signatures of mutagenesis in human cells

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The genetic material (DNA) in our cells is prone to change or mutation. From the moment of conception, the fertilized egg containing just a single copy of the human genome will have to be copied many thousands of times to make the trillions of cells in a human baby, potentially acquiring mutations each time it copies. In addition, the baby that is born and grows to adulthood will, through its life, be exposed to several internal DNA damaging agents, such as reactive by-products of cellular metabolism, as well as a variety of environmental DNA mutagens, such as ultraviolet radiation or chemical compounds. Our cells however, are equipped with DNA repair pathways to repair some of the damage.

Human cancers are known to be highly mutated entities with marked genetic differences when compared with the original genome at conception. The genome of a cancer will carry all the mutations that have been acquired by the cell that became the malignant clone, and is thus a historical record of the mutagenic and repair processes that have occurred through the life of the patient with cancer.

In this lecture, I will explain how we have used technological advances in reading the human genome, or sequencing, to explore all parts of the human genome. Capitalising on this surge in speed and scale of sequencing, we set out to show the mutagenic imprints, the signatures, caused by those internal and environmental mutagenic processes that have occurred throughout tumour development in cancer patients. In essence, we exploit the digital nature of modern sequencing technology and use mathematical methods to perform an archaeological excavation of cancer genomes, demonstrating the biological insights that have hitherto remain buried in the enormous and bewildering datasets of cancer genomes.

Given these advancing technologies and biological insights, what can we look forward to in the near future?

This talk is part of the Cambridge Philosophical Society series.

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