The biology of cancer Flashcards
What is cancer?
Canceris when abnormal cells divide in an uncontrolled way
The abnormal cells have the potential to:
- Form tumours
- Invade neighbouring tissues
- Spread through the body to distant tissues (metastasise)
What is normal cell division?
The body is made up of cells
Cells are differentiated to carry out different functions
New cells are generated by cell division
Cells receive positive signals to tell them when to divide:
- Growth factors and hormones
- Results in transcription
Normal cell division - signals to divide and not divide
A cell must receive positive signals telling it to divide e.g.
- Growth factors
- Hormones
There are also signals telling a cell not to divide
- Contact inhibition
- > You are surrounded by other cells- we don’t need new cells at the moment
- DNA damage response
- > Something is wrong with your DNA, don’t divide until it’s repaired
HOw is the process of cell division controlled?
The process of cell division is controlled by the cell cycle.
Range of signalling pathways that regulate this process, coded for my many genes
Checkpointd to check everything is fine -> mutation leads to cancer
Cellular DNA is constantly mutated
internal and external examples
Internal – reactive oxygen species
Internal – ineffective DNA repair mechanisms
External – Cigarette smoke, chemical consumption
External – UV light, ionising radiation
Cancer is an evolutionary process
Mutations may be acquired while the cell lineage is phenotypically normal, reflecting both the intrinsic mutations acquired during normal cell division and the effects of exogenous mutagens.
During the development of the cancer other processes, for example DNA repair defects, may contribute to the mutational burden.
Passenger mutations do not have any effect on the cancer cell, but driver mutations will cause a clonal expansion.
CLonal expansion is what leads to the tumour
Where does the mutation occur?
Constitutional/ germline
Somatic
When does the mutation occur?
Germline Present in the fertilised egg Present in every cell in the body Can be inherited from a parent Can be passed to offspring (BORN WITH)
Somatic Occurs after division of the fertilised egg Only present in a subset of cells Not inherited from a parent Occasionally passed to offspring (BY CHANCE)
Knudson’s two-hit hypothesis
Sporadic - Single tumour - Unilateral - Late onset (fertilised egg inherits no mutation, mutation in one copy of gene occassionally occurs as cells divide. Mutation in second copy of gene occurs)
Hereditary - Multiple tumours - Bilateral - Early onset (skipped the first mutation step as germline has a mutation. Therefore, fertilised egg has 50% chance of inheriting mutation. Mutation in one copy of gene is inherited in all body cells. Mutation in second copy of gene occurs)
Ways to crash a car or cause cancer
Jam the accelerator on
-> Oncogenes therefore keep cell cycle going with no stop
Cut the brake cable
-> tumour suppressor genes so won’t stop the cell cycle
Smash the car up so either of the above could go wrong at any point
-> DNA repair genes so build up more breaks and mutations
Oncogenes
‘Jam the accelerator on’
Proto-oncogenes & Oncogenes
All known proto-oncogenes are involved in positive control of cell growth and division.
Main classes include:
Class I: Growth Factors (grow)
Class II: Receptors for Growth Factors and Hormones (signal pathway)
Class III: Intracellular Signal Transducers
Class IV: Nuclear Transcription Factors
Class V: Cell-Cycle Control Proteins (check point)
Oncogenes are the mutated form of proto-oncogens
Proto-oncogenes are those which have the potential to become oncogenes which will keep cell cyle going on
Oncogenes - Dominant
Mutations relax cell control of growth, allowing unregulated proliferation – oncogenesis
Act as DOMINANT mutations at the cellular level
need chnage in one copy of the oncogene to have increased risk
Somatic Oncogenes
Chromosomal rearrangements in Leukaemia
Gene amplification in a range of cancers
Highlight importance that these are often reported somatic changes not in germline – not inherited – no need to refer to genetics
Germline oncogenes
Germline RET gene mutations in Multiple Endocrine Neoplasia Type 2 (MEN2)
Point mutations cause over-activation of RET – triggers proliferations in endocrine cells
Endocrine cancer syndrome
3 variants recognized
MEN2A/MEN2B/FMCT (familial medullary thyroid carcinoma)
All show high penetrance of medullary thyroid carcinoma
Autosomal dominant
Tumour suppressor genes
‘cut the break cable’
Two mutations (one on each allele) are required to inactivate tumor suppressor genes – i.e. mutations are RECESSIVE at the cellular level
seen more in inherited cancer
Lose one gene and you may have problems but won’t have cut off brakes
