Mechanisms Of Oncogenesis Flashcards
What is cancer the name for?
A group of diseases characterised by: Abnormal cell proliferation Tumour formation Invasion of neighbouring normal tissue Metastasis to form new tumours at distant sites
Where do carcinomas originate?
Epithelial cells
Where do sarcomas derive from?
Bone or muscle tissues
Where do adenosarcomas originate from?
Glandular tissue
What are the (many!) hallmarks of cancer?
Evading growth supressors Avoiding immune destruction Enabling replicative immortality Tumour-promoting inflammation Activating invasion and mutation Resisting cell death Deregulating cellular energetics Sustaining proliferative signalling
Why is cancer more prevelant the older you get?
Longer you live the more time there is for DNA to accumulate mutations that may lead to cancer
What do germline carcinogenic mutations cause?
An increased risk of developing cancer
What is cell proliferation caused by?
Growth factors
Cytokines
Hormones
What growth factors is cell proliferation caused by?
EGF, PDGF
What cytokines is cell proliferation caused by?
Growth hormones, interleukin
What are proto-onco genes?
Normal genes that can be activated to become oncogenes
What are oncogenes?
Proto-oncogenes that have been mutated in a way that leads to signals that cause uncontrolled growth
What do tumour supressor genes do?
Inhibit both growth and tumour formation
When do tumour supressor genes act?
In phase G1 of the cell cycle
What are the three assumptions that multistage carcinogenesis relies on?
Malignant transformation of a single cell is sufficient to give rise to a tumour
Any cell in a tissue is likely to be transformed as any other of the same type
Once a malignant cell is generated the mean time to tumour detection is generally constant
What are the names of the 5 models of carcinogenesis?
Chemical carcinogens Genome instability Non-genotoxic Darwinian Tissue organisation
What is the chemical carcinogen model of carcinogenesis?
Chemicals can alter initiation, promotion and progression to induce their carcinogenic effects
What is knudsons hypothesis for hereditary cancers based on?
Two-hit hypothesis
What is the two hit hypothesis?
At least two events are necessary for carcinogenesis and the cell with the first event must survive in the tissue long enough to sustain a second event
What are non-genotoxic modulators of risk?
Don’t seem to act through a structural change in DNA but rather through functional changes including epigenetic events
What is the mutation and selection model of clonal expansion?
Sequential accumulation of mutations due to carcinogen exposure
Tumour cells selected for ability to grow and invade
Selection includes resistance to therapy
What is the somatic mutation theory?
Cancer comes from a single somatic cell that has accumulated multiple DNA mutations
What is the tissue organisation field theory?
Carcinogenic agents destroy the normal tissue architecture that disrupt cell-cell signalling and comprising genomic integrity
What are the classes of carcinogens?
Chemical
Physical
Heritable
Viral
What are some examples of chemical carcinogens?
Polycyclic aromatic hydrocarbons Aromatic amines Nitrosamines Alkylating agents Carbamates Halogenated compounds Azo dyes
What are examples of physical carcinogens?
Radiation and asbestos
What are some viral carcinogens?
Hepatitis B
Epstein Barr
What does the ames test test for?
Chemical carcinogens
What is the ames test?
Test to determine the mutagenic activity of chemicals by observing whether they cause mutations in sample bacteria
What is the ames test method?
Add rat liver extract to a salmonella strain that requires histidine
Add a possible mutagen and spread over an agar plate that lacks histidine
In the ames test, what will happen if a mutagen is present?
Lots of colonies that have grown even in the absence of histidine
How do physical carcinogens work?
Act by imparting energy into biological material
What is the primary physical agent?
Radiation
How does radiation cause carcinogenesis?
Breaking DNA and causing pyrimidine dimers
What are heritable carcinogens generally?
Monogenic (mutation of a single gene)
What type of genes are mutated in heritable carcinogens?
Genes involved in controlling function of the cell cycle or the repair of DNA damage
What does a deficiency in DNA repair cause?
More DNA damages to occur -> inc risk for cancer
What DNA repair defect syndromes predispose you to cancer?
Ataxia telangiectasia Blooms syndrome Fanconis anaemia Li-fraumeni syndrome Lynch type II Xeroderma pigmentosum
What chromosomal abnormality syndromes predispose you to cancer?
Downs syndrome
Klinefelters syndrome
What is the mutated gene (and what does it code for) in ataxia telangiectasia?
ATM gene
Codes for a serine/threonine kinase that is recruited and activated by dsDNA breaks leading to cell cycle arrest, DNA repair and apoptosis
What is ataxia telangiectasia?
A disorder of neuromotor function and dilation of blood vessels
What types of cancer does ataxia telangiectasia predispose you to?
Lymphoma
Leukaemia
Breast cancer
What does blooms syndrome cause?
Short stature and skin rash after sun exposure
What gene is mutated in blooms syndrome (and what does it code for)?
BLM gene
Codes for a member of the RecQ helicase family that helps maintain the structure and integrity of DNA
What types of cancer does blooms syndrome predispose you to?
Skin cancer, basal cell carcinoma and squamous cell carcinoma
What are the mutations that cause lynch type?
MLH1, MSH2, MSH6 and PMS2
What does lynch type predispose you to?
Colorectal cancer
What are the properties of tumour-genic viruses?
Stable association with cells
Not kill cells
Evade immune surveillance of infected cells
How can viruses have a stable association with cells?
Chromosomal integration and changes in the epigenomes
How do viruses not kill cells?
Suppress the viral lytic cycle
How do viruses evade the immune surveillance of infected cells?
Immune supression and viral antigens not being expressed at cell surface
What cancer does epstein-barr virus cause?
Burkits lymphoma
What cancer does papilloma virus cause?
Cervical carcinoma
What cancer does hepatitis B and C virus cause?
Hepatoma
What cancer does HTLV-1 virus cause?
Adult T-cell leukaemia
Lymphoma
What are the three Es of cancer immunoediting?
Elimination, equilibrium and escape
