Genetic Changes in Cancer

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Cancer (otherwise defined medically as a malignant neoplasm) is a group of diseases which are associated with dynamic aberrations in the genome and consequent losses in the regulatory mechanisms which govern normal cell proliferation and homeostasis.

There are two important classes of genes involved in the control and homeostasis of the cell-cycle both of which play key roles with respect to cancer – the oncogenes and tumour-suppressor genes.

Oncogenic precursors known as proto-oncogenes are genes encoding proteins involved in signalling systems that control cell growth and differentiation – typically being involved in signal transduction pathways and execution of mitogenic signalling (Elliot and Elliot, 2009). Cancer cell mutations, or over expression, in proto-oncogenes generate oncogenic variants (alleles) which lead to what can be considered dominant 'gain of function' mutations endowing them with enhanced or novel functions relative to their proto-oncogene precursors (Fearon, 1999).

Tumour-suppressor genes on the other hand function as checkpoints in the cell-cycle (Elliot and Elliot, 2009). Mutations in tumour-suppressor genes, in contrast to oncogenes, lead to what can be considered recessive 'loss of function' defects inactivating their function and/or expression (Fearon, 1999). One tumour-suppressor gene of particular prominence – known as p53 – is sometimes referred to as 'the guardian of the genome' and acts to prevent genomic instability (Lane, 1992). In response to DNA damage p53 can elicit either arrest of the cell-cycle or induce apoptosis if the damage is too severe. Evidence has shown that the p53 gene is perhaps the single most frequently mutated gene in cancer being associated in over 50% of all...

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