Tumour Pathology 5

Question 1

How do tumour suppressor genes function?

Answer 1

Discourage cell growth or temporarily halt cell division to carry out DNA repair

Question 2

What is an anti-oncogene?

Answer 2

A tumour suppressor gene

Responsible for Apoptosis
DNA repair and the negative regulation of mitosis

Question 3

What do mutations in retinoblastoma gene cause?

Answer 3

Favour cell proliferation since it is an anti-oncogene (a tumour suppressor gene)

Question 4

What other mutations can cause the same effect of a mutated RB gene?

Answer 4

Mutational activation of Cyclin or CDK (naturally responsible for the phosphorylation of the pRB)

Mutational inactivation of CDKI’s

Question 5

What is the inherited form of oncogenesis?

Answer 5

One defective copy of the RB gene

Somatic point mutation of the other copy

Question 6

What is the sporadic form of oncogenesis?

Answer 6

Both hits occur in a single cell

Question 7

What portion of cancers are hereditary?

Answer 7

5-10% of all cancers

Question 8

Give two examples of inherited cancer syndromes?

Answer 8

Familial retinoblastomas

Familial adenomatous polyposis of colon

Question 9

What gene is responsible for signal transduction and also FAP colon cancer?

Answer 9

APC

Question 10

What gene is responsible for cell cycle regulation and causes retinoblastoma and osteosarcomas?

Answer 10

Rb

Question 11

What gene inhibits CDK’s and causes malignant melanoma?

Answer 11

p16 (INK4a)

Question 12

Which gene is responsible for DNA repair and causes breast and ovarian cancer?

Answer 12

BRCA 1/2

Question 13

What can cause alteration of proto-oncogene structure?

Answer 13

Point mutation

Chromosome rearrangements and translocations

Question 14

What can cause dysregulation of proto-oncogene expression?

Answer 14

Gene amplification

Overexpression

Question 15

Give examples of oncoprotein products

Answer 15

Growth factors
Growth factor receptors
Proteins involved in signal transduction
Nuclear regulatory proteins
Cell cycle regulators

Question 16

What mutation of the PDGF growth factor causes Astrocytoma and osteosarcoma’s?

Answer 16

Over expression

Question 17

What mutation of the growth factor receptor EGF causes Breast ovarian lung and stomach cancer?

Answer 17

Amplification

Question 18

What mutation in GTP binding signal transducaers causes lung, colon, pancreas, leukaemia

Answer 18

Point mutation

Question 19

What mutation in transcriptional activators (a nuclear regulatory protein) causes

Answer 19

Burkitt lymphoma

Question 20

What type of mutation are cell cycle regulators Cyclin D and CDK4 susceptible to?

Answer 20

Amplification

Cyclin D also susceptible to translocation

Question 21

What type of cancer can a mutation in Cyclin D cause?

Answer 21

Translocation - mantle cell lymphoma

Amplification - breast, liver, oesophageal

Question 22

What type of cancer does a mutation in cyclin dependant kinase cause?

Answer 22

melanoma, sarcoma

Question 23

What are the mechanisms of viral carcinogenesis?

Answer 23

Virus genome inserts near a host proto - oncogene

Viral promoter or other transcription regulator causes proto-oncogene over expression

Retroviruses insert oncogene into host DNA causing cell division.

Question 24

Chemical carcinogenesis involves adduct formation, what does this lead to?

Answer 24

Activation of oncogenes and suppression of anti-oncogenes

Question 25

What is a neoplasm?

Answer 25

A new and abnormal growth of tissue in the body.

Question 26

What is the function of the p16 protein?

Answer 26

It is an inhibitor of the CDK's which are involved in the phosphorylation of the of the pRB - progression from G1 to S phase

Question 27

What happens when pRB is bound to E2F?

Answer 27

The complex acts as a growth suppressor - prevents progression through the cell cycle When unbound - no inhibition exists - progression is possible.