100000 people 100 0 40 60 20 age of person in years

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Unformatted text preview: ells to accumulate enough mutations Cancer Risk and Aging 400 Colon 300 Breast Number of Cancer Cases 200 (per 100,000 people) 100 0 40 60 20 Age of Person (in years) 80 Microevolution of a cancer cell A series of mutations in a cell causes it to proliferate more than its immediate neighbours. As the cluster of dividing cells grows over time, further mutations turn atypical hyperplasia into a cancer (carcinoma). The spreading of cancer cells to other tissues and organs (metastasis) occurs when the adhesion of these cancerous cells breaks down, and they are able to travel easily to new locations. Characteristics of cancer cells • Different cancers require different combination of abnormal properties • Key characteristics of cancer cells: • Reduced dependence on signals from other cells for their growth, survival and division • E.g. Mutation in Ras gene can cause intracellular signal for proliferation to be produced even in absence of extracellular signal normally needed to trigger it • Resistance to apoptosis • Key characteristics of cancer cells (cont’): • Can proliferate indefinitely • Most cancer cells are genetically unstable => increased mutation rate • Abnormally invasive • Can survive and proliferate in foreign tissues to form secondary tumours (metastasis) Genes and Cancer • Cancer depends on accumulation of mutations and epigenetic changes in cells. • To understand cancer at a molecular level => need to identify the mutations and epigenetic changes involved => how they give rise to cancerous cell behaviour • Finding the cancerous cells is relatively easy, finding the small number of genes that promote cancer among all other genes in the cancerous cells – a challenge (needle in haystack) • Finding a gene responsible for any mutant phenotype is difficult, but for cancer – particularly complex • A typical cancer depends on a set of mutations and epigenetic changes (usually diff set in each individual patient) => introduction of any single gene into a normal cell is not enough to make cell cancerous • co-operation between different altered genes makes it difficult to test significance of any individual gene alteration • Cancer cells also have a large number of somatic mutations which are by-products of it genetic instability => difficult to distinguish meaningless changes from those with a real role • Despite difficulties, many genes repeatedly altered in human cancers (cancer-critical genes)...
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