Mechanisms of oncogenesis

Question 1

List the risks/prevention of cancer

Answer 1

Alcohol/smoking
Physical activity 
Diet/obesity
Inherited genes
Air pollution/radon
Infections and HPV
UV
Hormones

Question 2

What is cancer

Answer 2

Group of diseases characterised by:

Abnormal cell proliferation
Tumour formation
Invasion of neighbouring normal tissue
Metastasis to form new tumours at distant sites

Question 3

What are carcinomas

Answer 3

Epithelial cells ~85%

Cancer that develop from epithelial cells

Question 4

What are sarcomas

Answer 4

Cancer derived from mesoderm cells

Question 5

What are adenocarcinomas

Answer 5

Cancers in glandular tissue

Question 6

10 hallmarks of cancer

Answer 6

Evading growth suppressors 
Avoiding immune dysfunction
Enabling replicative immortality 
Tumor promoting inflammation
Activating invasion and metastasis 
Inducing angiogenesis
Genome instability & mutation 
Resisting cell death
Deregulating cellular genetics 
Sustaining proliferative signaling

Question 7

What do accumulation of mutations over time represent and when do they occur

Answer 7

The multi-step process that underlies carcinogenesis

Occurs after cells defence mech. of DNA repair evaded

Question 8

What causes cell to escape surveillance

Answer 8

Many mech for carcinogenesis block

But burdening increases possibility of cells escaping

Question 9

Link between age-cancer

Answer 9

Longer we live the more DNA mutations accumulate = may lead to cancer

Question 10

What is clonal development

Answer 10

All cells in primary tumour from single cell, intiation of cancer = clonal

Question 11

What allows for heterogeneity of cells in a tumour

Answer 11

Cells evolve - sub clonal selection = growth advantage

Question 12

What are tumour cells dependent on

Answer 12

On interaction w/other tumour cells + tumour microenvironment

Question 13

Explain the importance of control of cell division in self renewing tissues

Answer 13

Important in rapidly self renewing tissues when proliferation must balance cell loss

Question 14

Carcinogenesis - define

Answer 14

Initiation of cancer formation

Question 15

Proto-oncogenes - define

Answer 15

Normal genes activated to be oncogenic

Question 16

Oncogene - define

Answer 16

A mutated proto-O, leading to signals that cause uncontrolled growth

Question 17

Tumour suppressor genes - functions and describe effect once mutated

Answer 17

Inhibit both growth and tumour formation

Act as braking signals during phase G1 of the cell cycle, to stop or slow the cell cycle before S phase

If tumour-suppressor genes are mutated, the normal brake mechanism will be disabled, resulting in uncontrolled growth, i.e. cancer

Question 18

Describe 3 assumptions made about carcinogenesis

Answer 18

Malignant transformation of a single cell is sufficient to give rise to a tumour

Any cell in a tissue is as likely to be transformed as same type

Once malignant cell generated = mean time to tumour detection is generally constant

Question 19

Describe model 1 of carcinogenesis, its:
Focus
Mech
Models

Answer 19

Mutational

Focus = chemical carcinogens
- examples = viruses, tobacco, HPV

Mech = DNA adducts

Models = mutations, oncogenes + armitage-Doll

Question 20

DNA adducts - define

Answer 20

Covalent modifications of the DNA that result from exposure to specific carcinogens = can serve as biomarker

Question 21

Describe model 2 of carcinogenesis, its:
Focus
Mech
Models

Answer 21

Genome instability (GI)

Focus = familality + GI
- examples = colon cancer, Rb

Mech = CIN, MIN, MMR, BRCA1, TSG

Model = knudson

Question 22

Describe model 3 of carcinogenesis, its:
Focus
Mech
Models

Answer 22

Non-genotoxic

Focus = clonal expansion/epigenetics
- examples = diet, hormones

Mech = methylation, histone acetylation

Model = moolgavkar

Question 23

Describe model 4 of carcinogenesis, its:
Focus
Mech
Models

Answer 23

Darwinian

Focus = clonal expansion/cell selection

Examples = beta-carotene, folate, chemotherapy

Mech = selective advantage

Model = nowak

Question 24

Describe model 5 of carcinogenesis, its:
Focus
Mech
Models

Answer 24

Tissue organisation

Focus = microenvironment, morphostats

Model = baker

Question 25

Morphostat

Answer 25

Any biochemical compound responsible for the maintenance of normal tissue microarchitecture

Question 26

Describe the effect of carcinogens

Answer 26

Alter any of cancers’ processes to induce carcinogenic effects

Can induce DNA damage + act in genotoxic manner

Question 27

Explain the significance of the presence of multiple mutations in critical genes

Answer 27

Feature of cancer cells + supports that cancer arises through accumulation of irreversible DNA damage

Question 28

Describe the discovery of specific chemicals that can induce cancer

Answer 28

1915, Katsuburo Yamagiwa = rabbit ears repeatedly treated w/tar = cancer (chemicals = carcinogens)

1940, British chemists - purification of coal tar, proved ability to induce cancer on mice skin

Question 29

Describe the classes of carcinogens

Answer 29

Chemical = 10 groups = polycyclic aromatic hydrocarbons, aromatic amines,
azo dyes, nitrosamines, carbamates, halogenated compounds,
alkylating agents

Physical = radiation (ionizing/UV) and asbestos