Lecture 10 - Neoplasia III

Question 1

what are 3 examples of inherited susceptibility to development of tumours?

Answer 1

retinitis pigmentosum
ataxia telangiectasia
fanconi’s anaemia

Question 2

how does retinitis pigmentosum increase susceptibility to tumours?

Answer 2

increased risk of skin cancers when exposed to uv rays in sunlight

Question 3

how does ataxia telangiectasia increase susceptibility to tumours?

Answer 3

defective response to radiation damage
profound susceptibility to lymphoid malignancies
usually die before 20

Question 4

how does fanconi’s anaemia increase susceptibility to tumours?

Answer 4

sensitivity to dna cross linking agents, marrow hypo function and multiple congenital anomalies
predisposition to cancer

Question 5

which gene inheritance causes familial adenomatous polyposis?

Answer 5

apc

Question 6

which gene inheritance causes breast cancer?

Answer 6

brca 1/2

Question 7

which gene inheritance causes li fraumeni syndrome?

Answer 7

p53

Question 8

what is a proto oncogene?

Answer 8

a normal gene that can become an oncogene due to mutations or increased expression

Question 9

what is the dna sequence of a proto oncogene?

Answer 9

identical to viral oncogenes

Question 10

how do proto oncogenes become oncogenes?

Answer 10

mutation, amplification, translocation

Question 11

what are the products of oncogenes?

Answer 11

oncoproteins

Question 12

what is the significance of oncogenes?

Answer 12

cell can escape normal growth contro

lbecomes self sufficient - doesnt require external signals for growth

Question 13

how many alleles of a proto oncogene need to mutate to cause neoplasia?

Answer 13

one

Question 14

what is a tumour suppressor gene?

Answer 14

a gene that encodes proteins that suppress growth and therefore cancer

Question 15

what is the result of loss or alteration of tumour suppressor genes?

Answer 15

loss of growth suppression

Question 16

how many alleles of a tumour suppressor genes need to mutate to cause neoplasia?

Answer 16

two

Question 17

list three oncogenes

Answer 17

rasc-mycher-2

Question 18

what is the role of the ras oncogene?

Answer 18

normally transmits growth promoting signals to nucleus
mutant ras is permanently activated - continuous stimulation of cells
15-20% of all cancers
colon and lung cancer

Question 19

what is the role of the c-myc oncogene?

Answer 19

binds to dna, stimulates synthesis
amplified –> neuroblastoma, breast cancer
translocation from 8 to 14 –> burkitts lymphoma

Question 20

what is the role of the her-2 oncogene?

Answer 20

encodes for a growth factor receptor
amplified
25% of breast cancers

Question 21

what is a competitive antagonist at the her-2 receptor?

Answer 21

herceptin

Question 22

list two tumour suppressor genes

Answer 22

pRb

p53

Question 23

what is the role of pRb?

Answer 23

passage beyond R checkpoint at G1/S boundary is governed by phosphorylation of pRb
defect in both alleles leads to cell escaping cell cycle control
retinoblastoma

Question 24

what is the role of p53?

Answer 24

approx 50% of tumour contains p53 mutations
gene encodes a nuclear protein which binds to and modulates expression of genes important for cell cycle arrest, dna repair and apoptosis

Question 25

describe the initiator stage of carcinogenesis

Answer 25

1. exposure of cells to sufficient dose of initiator 2. cell is altered, potentially capable of producing a tumour 3. permanent dna damage 4. irreversible and has memory 5. effect modified by genetic factors 6. initiation is not sufficient for tumour formation

Question 26

describe the promoter stage of carcinogenesis

Answer 26

1. can induce tumours in initiated cells 2. non tumourigenic on their own 3. need exposure after initiation 4. cellular changes are reversible if remove promoter 5. enhance proliferations, especially in mutated cells and increase incidence of further mutations

Question 27

how does radiation contribute to tumour development?

Answer 27

dna damage: single strand break double strand break base damage

Question 28

what is the effect of radiation dependent on?

Answer 28

quality of radiation | dose

Question 29

give two types of radiation

Answer 29

ionising | ultraviolet

Question 30

how do chemicals contribute to tumour development?

Answer 30

act directly | require metabolic conversion to an active form

Question 31

give three examples that contribute to tumour development

Answer 31

polycyclic aromatic hydrocarbons aromatic amines alkylating agents

Question 32

how do polycyclic aromatic hydrocarbons contribute to tumour development?

Answer 32

produced in combustion of tobacco and fossil fuel hydroxylated to active form lung cancer, bladder cancer, skin cancer

Question 33

how do aromatic amines contribute to tumour development?

Answer 33

hydroxylated in liver and conjugated with glucorinic acid deconjugated to active form in urinary tract by urinary glucuronidase active form sits in bladder --> bladder cancer rubber and dye workers

Question 34

how do alkylating agents contribute to tumour development?

Answer 34

bind directly to dna | nitrogen mustard

Question 35

give three viruses that contribute to tumour development

Answer 35

hep b epstein barr human papilloma

Question 36

how does hep b contribute to tumour development?

Answer 36

associated with hepatocellular carcinoma viral dna integrated into host cell genome virus causes liver cell injury --> regenerative hyperplasia increased cell division gives increased risk of genetic changes

Question 37

how does epstein barr contribute to tumour development?

Answer 37

implicated in pathogenesis of burkitts lymphoma, some hodgkins lymphoma and nasopharyngeal carcinoma infects epithelial cells or oropharynx and B cells viral genes dysregulate normal proliferative and survival signals sets the stage for acquisition of mutations

Question 38

how does human papilloma contribute to tumour development?

Answer 38

hpv genes disrupt normal cell cycle | viral genes incorporated into host cell genome, driving proliferation

Question 39

give five other agents that contribute to tumour development

Answer 39

``` asbestos aflatoxins schistosoma helicobacter hormones ```

Question 40

what does asbestos cause?

Answer 40

malignant mesothelioma | lung cancer

Question 41

what do aflatoxins cause?

Answer 41

hepatocellular carcinoma

Question 42

what does schistosoma cause?

Answer 42

bladder cancer

Question 43

what does helicobacter cause?

Answer 43

gastric cancer | lymphoma

Question 44

what do hormones cause?

Answer 44

androgens | hepatocellular carcinoma

Question 45

give three conditions that predispose tumours

Answer 45

ulcerative colitis cirrhosis adenoma of colon/rectum