Hallmarks of Cancer I & II

Question 1

what is cancer?

Answer 1

a genetic disease characterised by unregulated cell proliferation, invasion and metastasis

Question 2

what is the difference between a benign mass and neoplasia?

Answer 2

tumour is benign if the neoplastic cells are clustered in a single mass, but malignant if they have undergone metastasis

Question 3

how do different cancers differ?

Answer 3

• tissue and cell type of origin
• causal factors
• molecular mechanisms

Question 4

what is a carcinoma?

Answer 4

cancer of epithelial origin - 85% of human cancers

Question 5

what is a sarcoma?

Answer 5

cancer of mesenchymal origin - bone, fat, muscle

Question 6

what is a leukaemia?

Answer 6

cancer of haemopoietic origin

Question 7

in what way is cancer a genetic disease?

Answer 7

cancer results from the accumulation of mutations with time. genetic changes creating oncogenes or LoF in tumour suppressor genes are responsible for creation of ‘hallmarks of cancer’

Question 8

what percentages of cancer are somatic, germline and familial?

Answer 8

somatic: 80%
familial: 10-15%
germline: 5-10%

Question 9

what is Li-Fraumeni syndrome?

Answer 9

hereditary cancer syndrome characterised by p53 LoF

Question 10

what environmental factors cause somatic genetic changes?

Answer 10

• infectious agents

- lifestyle

Question 11

why does the incidence of human cancer increase with age?

Answer 11

age is associated with increased exposure to mutagens - increased level of genetic mutation

Question 12

how does helicobacter pylori infection contribute to carcinogenesis?

Answer 12

creates a pro-inflammatory environment which promotes tumourigenesis

Question 13

what are tumour initiators?

Answer 13

substances that interact with and cause mutation to the DNA

• single exposure is enough, but effect is additive
• must be administered before the promoter
• irreversible
• use Ames test

Question 14

what are tumour promoters?

Answer 14

substances that interact with cells to promote growth and block differentiation

• not capable of initiation - doesn’t directly damage the DNA
• must be administered after initiator
• prolonged exposure is required
• reversible
• no test

Question 15

give some examples of tumour initiators

Answer 15

chemical carcinogens: polycyclic aromatic hydrocarbons, aromatic amines, azo dyes
ionising radiation
UV light

Question 16

what is the Ames Test?

Answer 16

a test for initiators (DNA damage) - ability of bacteria to grow in histidine deficient media shows mutation

Question 17

outline the Ames Test

Answer 17

1) incubate the test compound with rat liver homogenate
2) metabolic enzymes in rat liver homogenate activates test compounds
3) add mixture to histidine-deficient salmonella
4) count number of colonies

Question 18

what types of DNA repair are there?

Answer 18

• mismatch repair
• base excision repair
• nucleotide excision repair

Question 19

what do mismatch repair enzymes do?

Answer 19

repair nucleotides of normal structure in the wrong positions

Question 20

what does MGMT do?

Answer 20

methylguanine DNA methyltransferase removes methyl or ethyl adducts from the O(6) position of a guanine caused by alkylating agents such as ENU