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Types of genes which maymutate to cause cancer:
Tumour suppressor genes
oncogenes
DNA repair genes telomerase
p53
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Tumour suppressor genes
The genes normal function is to regulate cell division. Bothalleles need to be mutated or removed in order to lose the geneactivity.The first mutation may be inherited or somatic.The second mutation will often be a gross event leading to loss
of heterozygosity in the surrounding area.
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retinoblastoma
Retinoblastoma (RB) is a malignanttumor of the developing retina thatoccurs in children, usually before the
age of five years. All forms of retinoblastoma represent a
mutation in the gene RB1 located in inthe region 13q14.1-q14.2.
The gene is about 180 kb in length with27 exons that code for a transcript ofonly 4.7 kb.
individual mutations are
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oncogenes
Cellular oncogene c-onc
Viral oncogene v-onc
Proto-oncogene, activated bymutation to c-onc
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Mechanism Of OncogeneActivation
Method OfActivationOncogene
Amplification MYC, ERBB2
Insertional
mutagenesis
INT1, INT2
Translocation MYC
Structural alteration ABL, KRAS
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Proto-oncogene activation
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Types of proto-oncogene
Growth factore.g. SIS oncogene (PDGF)
Growth factor receptore.g. tyrosine kinase receptors
G proteins
e.g. ras Nuclear transcription factors
e.g. MYC
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Phosphorylation of RB
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p53
suppresses progression through thecell cycle in response to DNAdamage
initiates apoptosis if the damage tothe cell is severe acts as a tumour suppressor
is a transcription factor and onceactivated, it represses transcriptionof one set of genes (several of whichare involved in stimulating cellgrowth) while stimulating expressionof other genes involved in cell cycle
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P53: The Guardian of Genome
p53 located on chromosome 17p p53 functions as cell cycle checkpoint protein
It works alongside genes that have growth-suppressingactivities
It functions in the G1 phase of the cell cycle
p53 also induces apoptosis (programmed cell death)
p53 prevents or repairs gene amplification
p53 Interacts with DNA replication factor (RPA) and inhibitsits binding to ssDNA Inhibit DNA replication and growth
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Evading apoptosis
External triggersIntracellular triggersDeath receptors
CaspasesSensors (8, 9)Executioners (3)
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