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All genes whose alteration contributes to the causation or evolution of cancer by driving tumorigenesis
Oncogenes & tumour suppressor genes

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Binding of EGF results in intracellular signalling - mutation of the extracellular domain can result in receptors triggering the signal without EGF

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(gain of function mutation: protein hyperactivity | only one gene copy needs to be mutated) – corresponding normal form: proto-oncogene
Myc protein: act in the nucleus to stimulate cell growth and division – contribute to cancer by being overproduced in its normal form

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Two different chromosomes containing different genes get translocated (parts of both fuse together)
this gene undergoes further transcription and translation -> the protein made contains genetic information from both (can become hyperactive)

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Tumour suppressor gene: loss of function

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Tumour suppressor gene: loss of function

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(loss of function mutation: destroy cellular activity | generally recessive) – corresponding normal form: tumour suppressor gene

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Mutation in coding sequence: hyperactive protein

Mutation in regulatory: normal protein overproduced

Gene amplification: normal protein overproduced

Chromosome rearrangement: nearby regulatory DNA sequence causes normal protein to be overproduced OR fusion to actively transcribe gene produces hyperactive fusion protein

Example Myc:

overproduce of normal protein (regulatory mutation)

Burkitt's lymphoma:
translocation - sequence of one chromosome is cut, placed onto the other -> difference in length
B-lymphocytes
Myc gene https://youtu.be/BADXO2Tezhk

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Retinoblastoma – loss of function mutation present in one copy of Rb in every somatic cell

Hereditary: inherited one Rb gene - other gene mutated → retinoblastoma
Nonhereditary: inherit two good genes: both genes mutate → retinoblastoma

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Ras: family of proto-oncogenes

Monomeric GTPases that help transmit signals from cell-surface receptors to cell interior

Ras oncogenes contain point mutations that create hyperactive Ras protein that cannot shut off by hydrolysing its bound GTP to GDP

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Retinoblastoma – using chromosomal deletion, Rb gene was cloned and sequenced. Deletion or loss of function mutation present in one copy of Rb in every somatic cell → retinoblastoma (very rarely both copies can be destroyed, this is non-hereditary retinoblastoma)

Rb genes are also missing in several other types of cancer: carcinomas of lung, breast, bladder

Rb genes encode Rb protein: universal regulator of cell cycle -> when this loss of function occurs, Rb protein is no longer produced

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Karyotype contains 48 instead of normal 46 -> can cause cancer

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Cell starts off with one mutation -> gains more mutation each cell cycle (cells around will also have mutations) -> malignant
Loss/gain of function: loss of contact inhibition and uncontrollable replication

(refer to mutations and genetic instability

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Difference between genetic and epigenetic

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Difference between genetic and epigenetic

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genetic looks at change in DNA sequence
epigenetic look at other heritable changes (external)

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Mutations that provide selective growth advantage

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Neutral - play no role in cancer development

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Frequency of occurrence -
Drivers are influential thus happen only in a subset of the population
passengers are random

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Benign tumour: does not have ability to invade surrounding tissue

Malignant tumour: ability to invade surrounding tissue, often break lose from primary tumour and enter bloodstream/lymphatic vessels (metastases)

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DNA hypermethylation: adds methyl group on the DNA -> silences the gene

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Apc is a tumour suppressor gene: changes that lead to genetic and epigenetic instability are likely to arise early in tumour progression
K-Ras gene (monomeric GTPase) occur later, controls cell growth and cell death → no more conversion to GDP
p53 function allows cancer cells to endure stress and to avoid apoptosis and cell-cycle arrest → loss of p53 is related to the heightened activation

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p53: activated only in certain occasions - concentration of p53 only when hyperproliferative signals/DNA damage/telomere shortening/hypoxia occurs → p53 tell the cell to follow cell-cycle arrest/senescence/apoptosis

Mutation: weakens the ability of p53 → cannot combine to perform cell-cycle arrest/etc (example of loss of function)

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When it infects a cell its RNA genome is copied into DNA by reverse transcription and the DNA is inserted into the host genome (persists and is inherited by subsequent generations of cells)

Src – normal c-Src -> oncogene v-Src

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Takes a long time for an individual clone of cells to accumulate large number of mutations -> genetic instability -> interferes with accurate replication and maintenance of the genome -> increases the mutation rate
Changes of karyotype