L20 - Mechanisms of Oncogenesis Flashcards
(32 cards)
What is cancer?
A group of diseases characterised by abnormal cell proliferation, tumour formation, innvasion of neighbouring normal tissue and metastasis to form new tumours at distant sites.
What are carcinomas?
cancers that occur in epithelial cells
What are sarcomas?
cancers that occur in mesoderm cells like bone and muscle
What are adenocarcinomas?
cancers that are found in the glandular tissue
What is meant by a germline mutation?
a germline mutation is when there is a damage/change in the DNA of egg or sperm cells, perhaps due to point mutations or deletions. This mutation is inheritable and can be passed onto offspring. It rarely causes cancer immediatly however that person is at increased risk of developing cancer.
What is meant by somatic mutations?
Arises from a normal cell of the body, and cannot be passed onto offspring. It is however, passd onto the daughter cells each time the cell replicates. All cells of the tumour arise from one cell - developmental process of tumour is clonal
What are oncogenes?
Normal genes within cells that regulate growth. If an oncogene acquires a mutation in one of the alleles, it leads to signals that cause uncontrolled growth
What are tumour supressor genes?
They inhibit growth and tumour formation. They act as braking signals during phase G1 of the cell cycle to stop/slow cells before S phase.
There must be 2 individual mutations in the tumour supressor genes for them to malfunction. If they are mutated, the normal brake mechanism will be disabled, resulting in uncontrolled growth.
Describe Model 1 (chemical carcinogens) as a model of carcinogenesis?
MODEL 1 - CHEMICAL CARCINOGENS
Carcinogens affect any point of the muti-step process that is cancer, including the initiation, promotion and progression stages.
They work by altering the structure of DNA, and if this damage isn’t repaired, there will be an accumulation of damage
In the majority of instances, chemical caricnogens can induce this DNA damage and act in a genotoxic manner.
Four of the major groups: polycyclic aromatic hydrocarbons, aromatic amines, nitrosamines and alkylating agents exert their effects by adding functional groups to DNA bases called DNA adducts.
What are some examples of chemical carcinogens?
polyclyclic aromatic hydrocarbons
aromatic amines
azo dyes
nitrosamines
carbamates
halogenated compounds
alkylating agents
What are some examples of physical carcinogens?
Radiation (ionising or UV radiation)
Asbestos
What are some examples of heritable carcinogens?
genetic predisposition
What are some examples of viral carcinogens?
Hepatitis B
Epstein Barr
Describe Model 1 (physical carcinogens) as a model of carcinogenesis?
MODEL 1 - PHYSICAL CARCINOGENS
They act by imparting energy into the biological material and altering the bonding of molecules.
Ration is the primary physical agent. UV radiation does not penetrate further that the skin.
Radiation causes pyrimidine dimers and DNA breaks, which can be repaired. However if repair mechanims are mutated, it leads to worse damage like translocations and mutations.
What test can be used to test whether a chemical is a carcinogen?
The Ames test:
it is a test used to determine the mutagenic activity of chemicals by observing whether they cause mutations in sample bacteria.
Describe Model 1 (heritable carcinogens) as a model of carcinogenesis?
MODEL 1 - HERITABLE CARCIOGENS
Due to inherited germline mutations which increase the risk of developing cancer.
In most hereditary malignant syndromes, the elevated cancer risk is due to a mutation of a single gene ( these are monogenic hereditary diseases)
The affected genes usually have a controlling function on the cell cycle or DNA repair
Describe Ataxia Telangiectasia as a DNA repair defect disease?
neuromoto dysfunction, dilation of blood vessels and spider viens in the eyes.
Mutation in the ATM gene which codes for serine/threonine kinase that is recruited and activated by dsDNA breaks leading to to cell cycle arrest, DNA repair and apoptosis.
can lead to lymphoma, leukeamia and breast cancer
Describe Bloom’s syndrome as a DNA repair defect disease?
short statute, skin rash after exposure to the sun
Mutation in the BLM gene that provides instructions for coding a memeber of the RecQ helicase family that helps manitain the integrity and structure of DNA
leads to skin cancer, basal cell carcinoma, and squamous cell carcinoma
Describe Lynch type as a DNA repair defect disease?
LS dosent cuase any symptoms, the first sign that a person has it, is when symotoms of bowel and womb cancer develop.
Mutations in DNA mismatch repair genes, notable MLH1, MSH2, PMS2 and MSH6.
Can lead to Colorectal cancer
Describe Model 1 (viral carcinogens) as a model of carcinogenesis?
Most harm is caused when viruses multiply inside the infected cell, kill the cell and then release progeny to further infect other cells
Sometimes viruses can cause cancer, and this occurs during the later phase of infection, when there is restricted gene expression. This can incude oncogenes of the virus. It drives expression of genes that will cause transformation of the cell.
What are the poperties of tumourigenic viruses?
- have stable association with cells (chromosomal integration with cellular genes)
- Must not kill cells (has to supress the lytic cycle)
- has to evade the immune system’s surveillance of infected cells (genes expressed in later stages re non-immunogenic, so they won’t be detected by the immune system)
What are some DNA viruses that are associated with hman cancer?
Epstein-Barr Virus - lymphoma and nasopharyngeal cancer
Papilloma Viruses - cervical cancer and warts
Hepatitis B and C - hepatoma
What ar some RNA viruses that are associated with human cancer?
HLV - 1 : adult T-cell leukeamia and lymphoma
Describe Model 2 of Carcinogenesis?
genome instability and familiality.
On average 60,000 mutations can occur a day in the body, however they are usually repaired.
Knudson hypothesis:
he performed analysis on cases of the 2 types of retinoblastoma - the inherited type (familiar form) or the sporadic form. He found that patients with the sporadic form, developed the tumour much later in life than the inherited type patients.
