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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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