Cancer genetics Flashcards
What is cancer ?
cells that divide and proliferate uncontrollably due to alterations / mutations in DNA
Which genes do mutations occur in that lead to cancer?
mutations in
- Tumour suppressor genes causing them to be silenced
- Oncogenes being over-expressed
What three things cause cancer cells to proliferate?
- Self synthesis of growth factors
- signal nearby cells to produce growth factors
- increase responsitivity to growth factors
What protein do cancer cells develop that cause immune evasion?
Tumour cells contain a protein PD-L1 which effectively enables it to evade the immune system by down-regulating T cells
Bind to PD-1 receptor on the T- cell stopping it from attacking the cancerous cell
What are the differences between a benign tumour and malignant tumour?
Benign: Grows more slowly Well-differentiated Capsulated Does NOT invade neighbouring tissue Does NOT metastasize
Malignant: Grows faster Poorly differentiated Not capsulated Invades neighbouring tissue Invades basement membrane and metastasizes
What are three benign tumours of mesenchyme tissue?
Mesenchyme tissue
Osteoma (bone)
Chondroma (chondrocytes)
Angioma (blood vessels)
What are two benign tumours of epithelial tissue?
Papilloma (lining epithelial)
Adenoma (gland)
What is a malignant tumour of lymph nodes and blood cells?
Lymph nodes- Lymphoma
Blood cells- Leukaemia
What are three malignant tumours of mesenchyme tissue?
Angiosarcoma
Osteosatcoma
Chondrosarcoma
What are two malignant tumours of epithelial tissue?
squamous cell carcinoma
Adenocarcinoma
What can cause cancer?
- Chemicals from smoking
- radiation can damage genes
- exogenous factors (virus introducing genes into cells)
- heredity, alterations in genes can make someone more susceptible to cancer and can be passed on to the next generation
What did a study show that lifetime risk of developing cancer in a particular tissue correlates with?
Lifetime risk of developing cancer in a certain tissue correlates with how often stem cells divide in that tissue
What did a study show that lifetime risk of developing cancer in a particular tissue correlates with?
Lifetime risk of developing cancer in a certain tissue correlates with how often stem cells divide in that tissue
What is a germline mutation and can it passed onto offspring?
present in egg or sperm and are heritable, therefore can be passed onto offspring
rare 10% but every cell in the organism will contain that mutation, though tissue is affected at various levels
What is a somatic mutation and can it passed onto offspring?
Occur in non germline tissues and are non-heritable
much more common (90%)
Usually, mutation in cancer genes accumulate in somatic cells over many years until a cell accumulate a sufficient number of errors to initiate the tumour.
What is a passenger mutation?
Mutations a marker sign of cancer/driver mutations - many of these mutations can be tolerated by somatic cells
few mutations cause a selective advantage and are recurrently found
Mutations that provide no proliferative benefit
What is a driver mutation?
Anything that contributes to cancer growth
Confer a fitness advantage to somatic cells in their microenvironment
What are the 7 types of mutations?
deletions duplication Inversion translocation Single base substitution chromosome instability aneuploidy
What is an oncogene? What do they result in?
Pro oncogene that mutates to become an oncogene - single mutation tends to be sufficient for cancer development
can result in an increase of some form of protein activity or loss or regulation
What cellular processes does Ras protein control?
controls growth, migration, adhesion, cytoskeleton integrity, survival and differentiation
What is the specific Ras oncogene that is mutated and what happens when it is mutated?
k-Ras
Cell proliferation is disrupted and the cell starts to divide in an uncontrolled manner
What is the two hit hypothesis in cancer?
Situations where a form of genetic damage is not sufficient to enable cancer to develop (a second hit initiates cancer)
For example, a high degree of exposure to UV light may be required to initiate melanoma development.
What chromosomal rearrangement can lead to CML?
Creation of fusion genes with oncogenic potential
Philadelphia chromosome formed by translocation - a specific chromosomal abnormality - It is the results of a reciprocal translocation between chromosome 9 and chromosome 22.
Creates an elongated chromosome 9 and a truncated chromosome 22
the resulting Philadelphia translocation fuses two genes BCR and abl.
Give one function of retinoblastoma and explain how it carries out this function
Prevents excessive cell growth by inhibiting cell cycle progression until a cell has made all checks necessary in G1 phase
What phosphorylates retinoblastoma leading to its inactivation?
Cyclin dependent kinase
What does myc do?
transcription factor that increases expression of cyclins and cdks
How does normal Rb work?
Rb protein normally inhibits cell proliferation by binding and inhibiting transcription factor E2F which promotes transcription of cyclin E and CDK 2
Rb is only active and inhibiting E2F when it isn’t bound to phosphate so when growth factor stimulates a growth signalling pathway it activates CDKs which add a phosphate to rb inhibiting it
phosphorylated Rb releases E2 allowing cell proliferation to occur
What is the role of p53
P53 is a transcription factor that checks for DNA damage before a cell enters the S phase.
If there is damage, then specific protein kinases add phosphate groups to p53 - prolonging its life.
It binds to DNA and promotes transcription of a gene encoding protein called p21
p21 binds and inhibits the cyclin E-cyclin dependent kinase-2 protein complex, thus preventing passage from the G1 phase to S phase.
DNA repair proteins, also expressed thanks to p53 repairs the DNA damage
What 3 possible states can a cell that has accumulated a large amount of DNA, or one that no longer effectively repairs damage incurred to its DNA enter into?
An irreversible state of dormancy
Cell suicide, AKA apoptosis (programmed cell death)
Unregulated cell division, which can lead to the formation of a tumour that is cancerous
What virus is responsible for 99% of cervical cancer?
HPV (human papilloma virus) (However, not every viral infection leads to cancer and most HPV infections are lower risk and produce a localised disturbance)
