Genes and Cancer Flashcards
At a cellular level describe what cancer is.
The uncontrolled proliferation of cancer cells due to changes/mutations in the DNA of the genes which are critical for the control of cell growth, repair, and death.
What are the two types of mutations that can occur in the genes involved in cancer?
Aquired/somatic - most common. Due to a random mutation in the cell or due to exposure to a mutagen/ carcinogen
Inherited - less common. This is seen in familial cancer syndromes eg familial polyposis syndrome.
Describe the “two hit hypothesis”
The two hit hypothesis is seen in many of the familial cancer syndromes. This is the idea that there is a required loss of both alleles in a gene before a malignant phenotype occurs. Eg, someone may inherit a mutated allele from their mum but the normal allele will allow for normal functioning of that gene protein until that second allele is “knocked out”.
Hit one = an inherited germline mutation
Hit two = a deletion/mutation in the other copy of the gene
A common example of where this occurs is in Retinoblastoma in children.
Name/describe the four main types of genes involved in cancer
Oncogenes -
Genes that promote cell growth and proliferation
Tumour suppressive genes -
Genes that control cell growth
Genes involved in regulation of apoptosis -
Genes that prevent the accumulation of abnormal cells
Genes involved in DNA fixing mechanisms -
Fixes mismatches that occur after DNA replication.
What is epigenetics?
Epigenetics is the study of heritable changes in gene expression that does not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes.
Epigenetic changes are those that occur in the way that DNA is packaged, eg methylation - a methyl group is added which alters the DNA expression.
There is a lot of interest in developing drugs which target epigenetic factors.
Oncogenes are dominant transforming genes: what does this mean?
Dominant transforming genes are those that only require one allele of a gene to be mutated in order to change the cell.
What is the difference between an oncogene and a proto-oncogene?
A proto-oncogene is a normal gene that is carefully regulated and is only switched on when the cell is replicating. Most are involved in signal transduction pathways. They act to accelerate cells through the G1/growth phase of the cell cycle.
An oncogene is a mutated/activated proto-oncogene which stimulates cell proliferation even when the cell is not undergoing replication.
What are normal cells transformed into when proto-oncogenes are activated to oncogenes?
Neoplastic cells
Where in the growth pathway can proto-oncogenes act?
Anywhere from the start to end:
- Growth factors
- Growth factor receptors
- Signal transduction pathways
- Nuclear transcription factors
What are the different ways in proto-oncogenes are activated?
Gene amplification -
Increased number of actual copies of the gene on a chromosome
Over expression of the gene -
eg mutation to promoter may causes excessive expression
Point mutations -
eg RAS point mutations are seen in a large number of cancers
Gene rearrangement or translocation -
eg a translocation causes a gene to move to a promoter region or two genes get moved close together and they form a fusion gene or one gene is put under the influence of the other
Epigenetic changes -
eg a methyl group is removed from a gene allowing an inactive/silenced gene to become active
An example of gene amplification activating proto-oncogenes is in breast cancer. Describe what gene this is and how it occurs + how it could be picked up in a FISH study (fluorescence study of a chromosome)
HER-2 is a proto-oncogene that encodes for a growth factor receptor in breast cells.
In a lot of cancer patients this is over-expressed due to amplification of the HER-2 gene. It signals for proliferation of the cells which makes the tumours grow more aggressively.
In a FISH study of biopsy of breast tissue, you would see in one chromosome there is not two alleles glowing for the HER-2 gene but there is many many copies of the HER-2 gene.
Describe the translocation that occur in patients with burkitts lymphoma (the rare cancer where cells are dividing every 24 hours).
There is a translocation between chromosomes 8 and 14 whre the myc gene is moved close to a promoter region that is always active.
Using a car as an analogy - describe proto-oncogenes and tumour suppressive genes
Proto-oncogenes are the accelrators
Tumour suppresive genes are the brakes
Are tumour suppressive genes dominant or recessive acting?
Recessive - they usually require inactivation of both alleles hence they require “two hits”
What is a common gene that blocks apoptosis?
p53
