Molecular Biology and Cancer Prevention, Detection and Therapeutics

Question 1

Give three examples of DNA viruses and the tumours they may give rise to

Answer 1

1. Papovavirus family - give rise to warts (benign) or carcinoma of the uterine cervix
2. Hepadnavirus family e.g hepatitis B virus - liver cancer (hepatocellular carcinoma)
3. Herpesvirus family - give rise to nasopharyngeal carcinoma or Burkitt’s lymphoma

Question 2

Give two examples of RNA viruses and the tumours they may give rise to

Answer 2

Retrovirus family; adult T-cell leukaemia/ lymphoma

Human immunodeficiency virus; Karposi’s sarcoma

Question 3

Retroviral oncogenes are

Answer 3

genes ‘hijacked’ from host cells. A typical retrovirus does not contain any oncogenes. However, cellular genes can be acquired when the viral genome inserts/ excises from a host genome. They become overactive, as they are now under control from viral promoters

Question 4

Explain how DNA virus oncogenes work on permissive hosts and what their requirements are in order to get their own DNA copied.

Answer 4

DNA viruses require their host to be actively proliferating in order to get their own DNA copied. For this purpose they carry unique genes whose products interfere with the cell cycle’s control mechanisms.
This is not a problem for the host as it is going to be killed by lysis, however in non-permissive hosts, oncogenes persist.

Question 5

The effect of DNA viruses on
a) permissive host cells
b) non-permissive host cells
Which of the two leads to transformation?

Answer 5

a) When a virus infects a natural, permissive host, it replicates, causes cell lysis and releases progeny virus particles
b) In a non-permissive host, virus replication is blocked. Virus becomes permanently inserted into the host genome
NON-PERMISSIVE

Question 6

Mode of action of DNA virus oncogenes is to..

Answer 6

bind two of the most critical tumour suppressors of mammalian cells:
p53 and pRB

Question 7

What is p53 responsible for?

Answer 7

Involved in cell cycle arrest or apoptosis following DNA damage

Question 8

What is pRB involved in?

Answer 8

controlling the transcription of cyclin E and A at the restriction point

Question 9

What are two tumour suppressors?

Answer 9

p53 and pRB

Question 10

Rb protein binds to what, rendering it inactive?

At the same time, p53 protein activates safety brake on cell proliferation.

Answer 10

cell proliferation factor

Question 11

DNA virus oncogenes bind to _____ suppressors. They sequester ___ and _53, thus activating the cell proliferation factor and thus allowing gene transcription and cell proliferation to occur

Answer 11

tumour
Rb
p

Question 12

Papillomavirus uses two viral proteins __ and ___ to sequester the host cells p53 and Rb respectively

Answer 12

E6

E7

Question 13

CAUSES OF CERVICAL CANCER:
HPV infections (common) can either be a transient (most are cleared) or \_\_\_\_\_\_\_ infection. Need to have a \_\_\_\_\_\_\_ infection for aroun 10-20 years with a \_\_\_-\_\_\_\_ strain in order to develop \_\_\_\_\_\_\_\_ cancer. Other risk factors such as \_\_\_\_ and \_\_\_\_\_\_\_\_\_ also play a role.

Answer 13

persistent. 
high-risk
cervical.
age at infection
immunological factors

Question 14

What allows for detection of cervical cancer to be detected early?

Answer 14

Routine cervical smears

Question 15

What are the three results from cervical smears? - normal, precancerous lesion and invasive carcinoma

Answer 15

Normal: cells large and well differentiated
Precancerous lesion: Cell differentiation and proliferation is abnormal but lesion is not yet invasive, Cells are in different stages of differentiation, some quite immature.
Invasive carcinoma: All cells undifferentiated with scanty cytoplasm and relatively large nucleus

Question 16

What is a papilloma virus vaccination to prevent cervical cancer? Which HPV types does it protect against. How long is it the protection effective for?

Answer 16

Gardasil
HPV 6 and 11 (cause 90% of genital warts)
HPV 16 and 18
at least 8 years after completion of the three-dose course,

Question 17

Other than routine cervical smears, what is another method of cancer prevention/ early detection. When would this be carried out? Knowledge of carrier status can be used to inform?

Answer 17

Susceptibility genes
If you have a family history of particular types of cancer e.g. BRCA-related breast cancer or familial colon cancer.
- screening
- chemoprevention
- prophylactic surgery

Question 18

Why is it important to know the genotype of a tumour?

Targeted therapies only work if..

Answer 18

Knowing where the tissue of origin or whether a cancer is benign or malignant does not tell us about their characteristics/ how they behave and how to kill them. Tumours from the same origin can be genetically diverse and therefore behave in different ways.
The genetic profile of a tumour can tell us a lot about cell behaviour and therefore can inform both prognosis and treatment choice.
Targeted therapies will only work if the tumour actually possess the oncogene variant they target.

Question 19

How can some cancers become drug resistant?

Answer 19

Mutations in drug target (CML?imatinhib)

Mutations in genes in associated pathways (metabolising enzymes)

Question 20

TUMOUR GENOTYPING

You can use genomic, ________ and proteomic profiles to determine:

Answer 20

transriptomic

1. classify the tumour according to mutation profile
2. associate this profile with the ‘aggressiveness’ of the cancer and draw conclusion about the patients prognosis and best way to treat the tumour
3. Predict which treatment the tumour will best respond to