Mechanisms Of Oncogenesis Flashcards

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1
Q

What is cancer the name for?

A
A group of diseases characterised by:
Abnormal cell proliferation
Tumour formation
Invasion of neighbouring normal tissue
Metastasis to form new tumours at distant sites
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2
Q

Where do carcinomas originate?

A

Epithelial cells

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3
Q

Where do sarcomas derive from?

A

Bone or muscle tissues

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4
Q

Where do adenosarcomas originate from?

A

Glandular tissue

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5
Q

What are the (many!) hallmarks of cancer?

A
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
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6
Q

Why is cancer more prevelant the older you get?

A

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

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7
Q

What do germline carcinogenic mutations cause?

A

An increased risk of developing cancer

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8
Q

What is cell proliferation caused by?

A

Growth factors
Cytokines
Hormones

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9
Q

What growth factors is cell proliferation caused by?

A

EGF, PDGF

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10
Q

What cytokines is cell proliferation caused by?

A

Growth hormones, interleukin

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11
Q

What are proto-onco genes?

A

Normal genes that can be activated to become oncogenes

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12
Q

What are oncogenes?

A

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

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13
Q

What do tumour supressor genes do?

A

Inhibit both growth and tumour formation

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14
Q

When do tumour supressor genes act?

A

In phase G1 of the cell cycle

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15
Q

What are the three assumptions that multistage carcinogenesis relies on?

A

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

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16
Q

What are the names of the 5 models of carcinogenesis?

A
Chemical carcinogens
Genome instability
Non-genotoxic
Darwinian
Tissue organisation
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17
Q

What is the chemical carcinogen model of carcinogenesis?

A

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

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18
Q

What is knudsons hypothesis for hereditary cancers based on?

A

Two-hit hypothesis

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19
Q

What is the two hit hypothesis?

A

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

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20
Q

What are non-genotoxic modulators of risk?

A

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

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21
Q

What is the mutation and selection model of clonal expansion?

A

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

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22
Q

What is the somatic mutation theory?

A

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

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23
Q

What is the tissue organisation field theory?

A

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

24
Q

What are the classes of carcinogens?

A

Chemical
Physical
Heritable
Viral

25
Q

What are some examples of chemical carcinogens?

A
Polycyclic aromatic hydrocarbons
Aromatic amines
Nitrosamines
Alkylating agents
Carbamates
Halogenated compounds
Azo dyes
26
Q

What are examples of physical carcinogens?

A

Radiation and asbestos

27
Q

What are some viral carcinogens?

A

Hepatitis B

Epstein Barr

28
Q

What does the ames test test for?

A

Chemical carcinogens

29
Q

What is the ames test?

A

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

30
Q

What is the ames test method?

A

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

31
Q

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

A

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

32
Q

How do physical carcinogens work?

A

Act by imparting energy into biological material

33
Q

What is the primary physical agent?

A

Radiation

34
Q

How does radiation cause carcinogenesis?

A

Breaking DNA and causing pyrimidine dimers

35
Q

What are heritable carcinogens generally?

A

Monogenic (mutation of a single gene)

36
Q

What type of genes are mutated in heritable carcinogens?

A

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

37
Q

What does a deficiency in DNA repair cause?

A

More DNA damages to occur -> inc risk for cancer

38
Q

What DNA repair defect syndromes predispose you to cancer?

A
Ataxia telangiectasia
Blooms syndrome
Fanconis anaemia
Li-fraumeni syndrome
Lynch type II
Xeroderma pigmentosum
39
Q

What chromosomal abnormality syndromes predispose you to cancer?

A

Downs syndrome

Klinefelters syndrome

40
Q

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

A

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

41
Q

What is ataxia telangiectasia?

A

A disorder of neuromotor function and dilation of blood vessels

42
Q

What types of cancer does ataxia telangiectasia predispose you to?

A

Lymphoma
Leukaemia
Breast cancer

43
Q

What does blooms syndrome cause?

A

Short stature and skin rash after sun exposure

44
Q

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

A

BLM gene

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

45
Q

What types of cancer does blooms syndrome predispose you to?

A

Skin cancer, basal cell carcinoma and squamous cell carcinoma

46
Q

What are the mutations that cause lynch type?

A

MLH1, MSH2, MSH6 and PMS2

47
Q

What does lynch type predispose you to?

A

Colorectal cancer

48
Q

What are the properties of tumour-genic viruses?

A

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

49
Q

How can viruses have a stable association with cells?

A

Chromosomal integration and changes in the epigenomes

50
Q

How do viruses not kill cells?

A

Suppress the viral lytic cycle

51
Q

How do viruses evade the immune surveillance of infected cells?

A

Immune supression and viral antigens not being expressed at cell surface

52
Q

What cancer does epstein-barr virus cause?

A

Burkits lymphoma

53
Q

What cancer does papilloma virus cause?

A

Cervical carcinoma

54
Q

What cancer does hepatitis B and C virus cause?

A

Hepatoma

55
Q

What cancer does HTLV-1 virus cause?

A

Adult T-cell leukaemia

Lymphoma

56
Q

What are the three Es of cancer immunoediting?

A

Elimination, equilibrium and escape