Mechanisms Of Oncogenesis

Question 1

What is cancer the name for?

Answer 1

A group of diseases characterised by:
Abnormal cell proliferation
Tumour formation
Invasion of neighbouring normal tissue
Metastasis to form new tumours at distant sites

Question 2

Where do carcinomas originate?

Answer 2

Epithelial cells

Question 3

Where do sarcomas derive from?

Answer 3

Bone or muscle tissues

Question 4

Where do adenosarcomas originate from?

Answer 4

Glandular tissue

Question 5

What are the (many!) hallmarks of cancer?

Answer 5

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

Question 6

Why is cancer more prevelant the older you get?

Answer 6

Longer you live the more time there is for DNA to accumulate mutations that may lead to cancer

Question 7

What do germline carcinogenic mutations cause?

Answer 7

An increased risk of developing cancer

Question 8

What is cell proliferation caused by?

Answer 8

Growth factors
Cytokines
Hormones

Question 9

What growth factors is cell proliferation caused by?

Answer 9

EGF, PDGF

Question 10

What cytokines is cell proliferation caused by?

Answer 10

Growth hormones, interleukin

Question 11

What are proto-onco genes?

Answer 11

Normal genes that can be activated to become oncogenes

Question 12

What are oncogenes?

Answer 12

Proto-oncogenes that have been mutated in a way that leads to signals that cause uncontrolled growth

Question 13

What do tumour supressor genes do?

Answer 13

Inhibit both growth and tumour formation

Question 14

When do tumour supressor genes act?

Answer 14

In phase G1 of the cell cycle

Question 15

What are the three assumptions that multistage carcinogenesis relies on?

Answer 15

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

Question 16

What are the names of the 5 models of carcinogenesis?

Answer 16

Chemical carcinogens
Genome instability
Non-genotoxic
Darwinian
Tissue organisation

Question 17

What is the chemical carcinogen model of carcinogenesis?

Answer 17

Chemicals can alter initiation, promotion and progression to induce their carcinogenic effects

Question 18

What is knudsons hypothesis for hereditary cancers based on?

Answer 18

Two-hit hypothesis

Question 19

What is the two hit hypothesis?

Answer 19

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

Question 20

What are non-genotoxic modulators of risk?

Answer 20

Don’t seem to act through a structural change in DNA but rather through functional changes including epigenetic events

Question 21

What is the mutation and selection model of clonal expansion?

Answer 21

Sequential accumulation of mutations due to carcinogen exposure
Tumour cells selected for ability to grow and invade
Selection includes resistance to therapy

Question 22

What is the somatic mutation theory?

Answer 22

Cancer comes from a single somatic cell that has accumulated multiple DNA mutations

Question 23

What is the tissue organisation field theory?

Answer 23

Carcinogenic agents destroy the normal tissue architecture that disrupt cell-cell signalling and comprising genomic integrity

Question 24

What are the classes of carcinogens?

Answer 24

Chemical
Physical
Heritable
Viral

Question 25

What are some examples of chemical carcinogens?

Answer 25

``` Polycyclic aromatic hydrocarbons Aromatic amines Nitrosamines Alkylating agents Carbamates Halogenated compounds Azo dyes ```

Question 26

What are examples of physical carcinogens?

Answer 26

Radiation and asbestos

Question 27

What are some viral carcinogens?

Answer 27

Hepatitis B | Epstein Barr

Question 28

What does the ames test test for?

Answer 28

Chemical carcinogens

Question 29

What is the ames test?

Answer 29

Test to determine the mutagenic activity of chemicals by observing whether they cause mutations in sample bacteria

Question 30

What is the ames test method?

Answer 30

Add rat liver extract to a salmonella strain that requires histidine Add a possible mutagen and spread over an agar plate that lacks histidine

Question 31

In the ames test, what will happen if a mutagen is present?

Answer 31

Lots of colonies that have grown even in the absence of histidine

Question 32

How do physical carcinogens work?

Answer 32

Act by imparting energy into biological material

Question 33

What is the primary physical agent?

Answer 33

Radiation

Question 34

How does radiation cause carcinogenesis?

Answer 34

Breaking DNA and causing pyrimidine dimers

Question 35

What are heritable carcinogens generally?

Answer 35

Monogenic (mutation of a single gene)

Question 36

What type of genes are mutated in heritable carcinogens?

Answer 36

Genes involved in controlling function of the cell cycle or the repair of DNA damage

Question 37

What does a deficiency in DNA repair cause?

Answer 37

More DNA damages to occur -> inc risk for cancer

Question 38

What DNA repair defect syndromes predispose you to cancer?

Answer 38

``` Ataxia telangiectasia Blooms syndrome Fanconis anaemia Li-fraumeni syndrome Lynch type II Xeroderma pigmentosum ```

Question 39

What chromosomal abnormality syndromes predispose you to cancer?

Answer 39

Downs syndrome | Klinefelters syndrome

Question 40

What is the mutated gene (and what does it code for) in ataxia telangiectasia?

Answer 40

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

Question 41

What is ataxia telangiectasia?

Answer 41

A disorder of neuromotor function and dilation of blood vessels

Question 42

What types of cancer does ataxia telangiectasia predispose you to?

Answer 42

Lymphoma Leukaemia Breast cancer

Question 43

What does blooms syndrome cause?

Answer 43

Short stature and skin rash after sun exposure

Question 44

What gene is mutated in blooms syndrome (and what does it code for)?

Answer 44

BLM gene Codes for a member of the RecQ helicase family that helps maintain the structure and integrity of DNA

Question 45

What types of cancer does blooms syndrome predispose you to?

Answer 45

Skin cancer, basal cell carcinoma and squamous cell carcinoma

Question 46

What are the mutations that cause lynch type?

Answer 46

MLH1, MSH2, MSH6 and PMS2

Question 47

What does lynch type predispose you to?

Answer 47

Colorectal cancer

Question 48

What are the properties of tumour-genic viruses?

Answer 48

Stable association with cells Not kill cells Evade immune surveillance of infected cells

Question 49

How can viruses have a stable association with cells?

Answer 49

Chromosomal integration and changes in the epigenomes

Question 50

How do viruses not kill cells?

Answer 50

Suppress the viral lytic cycle

Question 51

How do viruses evade the immune surveillance of infected cells?

Answer 51

Immune supression and viral antigens not being expressed at cell surface

Question 52

What cancer does epstein-barr virus cause?

Answer 52

Burkits lymphoma

Question 53

What cancer does papilloma virus cause?

Answer 53

Cervical carcinoma

Question 54

What cancer does hepatitis B and C virus cause?

Answer 54

Hepatoma

Question 55

What cancer does HTLV-1 virus cause?

Answer 55

Adult T-cell leukaemia | Lymphoma

Question 56

What are the three Es of cancer immunoediting?

Answer 56

Elimination, equilibrium and escape