Types of genes which may mutate 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. Both alleles need to be mutated or removed in order to lose the gene activity. 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 malignant tumor of the developing retina that occurs in children, usually before the age of five years. All forms of retinoblastoma represent a mutation in the gene RB1 located in in the region 13q14.1-q14.2. The gene is about 180 kb in length with 27 exons that code for a transcript of only 4.7 kb. individual mutations are 3/13/13

oncogenes

Cellular oncogene c-onc Viral oncogene v-onc Proto-oncogene, activated by mutation to c-onc

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Mechanism Of Oncogene Activation

Method Of Activation Oncogene Amplification Insertional mutagenesis Translocation
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MYC, ERBB2 INT1, INT2

MYC ABL, KRAS

Proto-oncogene activation

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Types of proto-oncogene

Growth factor e.g. SIS oncogene (PDGF) Growth factor receptor e.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 the cell cycle in response to DNA damage initiates apoptosis if the damage to the cell is severe acts as a tumour suppressor is a transcription factor and once activated, it represses transcription of one set of genes (several of which are involved in stimulating cell growth) while stimulating expression 3/13/13 of other genes involved in cell cycle

P53: The Guardian of Genome

p53 located on chromosome 17p p53 functions as cell cycle checkpoint protein It works alongside genes that have growth-suppressing activities 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 inhibits its binding to ssDNA Inhibit DNA replication and growth

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Evading apoptosis
External triggers Intracellular triggers Death receptors Caspases
Sensors (8, 9) Executioners (3)

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