Tumour pathology 5

Question 1

What do tumour-supressor genes normally do?

Answer 1

• Negatively regulate mitosis (Rb gene)
• Regulate Apoptosis (p53)
• Regulate DNA repair (p53)

Question 2

What do proto-oncogenes do?

Answer 2

Normal genes that Codes for normal growth resulting proteins (growth factors and receptors)

Question 3

How does the Rb gene negatively regulate mitosis?

Answer 3

Rb gene codes for pRb

Activates and Loses its affinity for E2F transcription factor (which promotes DNA synthesis)

Question 4

What other mutations can mimic pRb loss?

Answer 4

• Mutational activation of Cyclin D or CDK4 (their complex phosphorylates and deactivates pRb)
• Mutational inactivation of CDK inhibitors

Question 5

What does Cyclin D/CDK4 complex normally do?

Answer 5

Phosphorylates pRb causin it to deactivate.
Allows E2F to promote cell division
[Occurs when external stimuli signal for mitosis to occur]

Question 6

Another name for Tumour-Supressor genes?

Answer 6

Anti-Oncogenes

Question 7

whats the two-hit hypothesis:?

Answer 7

Two mutations are required to inactivate tumour-suppresor genes

Question 8

What are the two forms of oncogenesis? (mutation to anti-oncogenes)

Answer 8

Sporadic (over time)

Inherited (early age)

Question 9

Explain inherited oncogenesis:

Answer 9

• One allele of Rb gene is inherited defective

- The Other copy undergoes somatic point mutation

Question 10

Explain sporadic oncogenesis?

Answer 10

Both ‘hits’ or mutations occur in a single cell

Question 11

Whats the difference between an inherited cancer syndrome and a familial cancer?

Answer 11

Inherited Cancer syndrome:

• Strong family histroy of unusual cancers
• Autosomal Dominant inheritance of a single mutant gene

Familial Cancer:

• Family cluster of cancers
• Multifactorial inheritance
• Individual predisposition is unclear

Question 12

Examples of inherited cancer syndromes?

Answer 12

• Familial Retinoblastoma

- FAP

Question 13

Examples of Familial Cancers:

Answer 13

Some breast or ovarian cancers

Question 14

How can an proto-oncogene become an oncogene?

Answer 14

• Mutation causes altered structure
• Dysregulation of expresssion by gene
• overexpression

Question 15

What do oncogenes code for?

Answer 15

Oncoproteins

e.g. growth factors, nuclear regulatory proteins, cell cycle regulators

Question 16

What are the mechanisms of viral carcinogneneiss?

Answer 16

• Retrovirus inserts oncogene into host DNA

- Viral promoter causes pro-oncogene over expression

Question 17

Examples of DNA viruses known to cause cancer?

Answer 17

• HEP B - Liver Cancer
• Herpes (epstein-barr specifcally) - Burkitt Lymphoma
• HPV - Cervical Cancer

Question 18

Mechanism of chemical carcinogenesis:

Answer 18

• > Chemical reacts iwth DNA to form DNA adducts
• > DNA adducts at particular chromosome sites leads to :
• > Oncogene activation or tumour-supressor gene deactivation

Question 19

What kind of mutations occur in most cancers?

Answer 19

• Activation or several oncogenes

- & loss of 2 or more anti-oncogenes

Question 20

Stages of carcinogenesis:

Answer 20

• Normal Cell
• DNA damage
• GEnomic mutation
• Oncogene activation/anti-oncogene supression
• Dysregulation
• Tumour progression
• Malignant Neoplasm

Question 21

Define oncogenes

Answer 21

cancer causing genes (derived from proto-oncogenes)

Question 22

What is key to forming malignant neoplasms?

Answer 22

Loss or mutations of p53 allows genetically damaged cells to proliferate

Question 23

What causes radiation carcinogenesis?

Answer 23

• Purine and pyridine bases in DNA are critical targets for radiation damage
• High energy radiation is carcinogenic if received in sufficient doses

(UV, X-rays, gamma radiation)