Molecular Pathology of Tumours

Question 1

what are the four properties of malignant cells

Answer 1

disordered proliferation
disordered apoptosis
disordered differentiation
disordered relationship between proliferating cells and surrounding environment

Question 2

what are the 5 stages of malignant spread

Answer 2

normal 
dysplasia 
carcinoma in situ 
invasion 
metastasis

Question 3

what are the two types of cells that are mutated

Answer 3

• oncogene activation

- tumour supressor gene inactivation

Question 4

oncogenes

Answer 4

• drivers of neoplastic behaviour
• porto-oncogene are the inactive form which is then activated to form oncogenes
  these stimulates cell survival and proliferation

Question 5

what are the three ways that proto-oncogenes are converted to oncogenes

Answer 5

• mutation in coding sequence = hyperactive protein made in normal amounts
• gene amplification = normal protein greatly overproduced
• chromosome rearrangement = nearby regulatory DNA sequence causes normal protein to be overproduced / fusion to actively transcribed gene produces hyperactive fusion protein

Question 6

What can oncogenes do

Answer 6

effect:
growth factor - sis
growth factor receptor - HER2
signal transducer - ras
transcription factor - myc

Question 7

effect of oncogenes in the nucleus

Answer 7

direct stimulation of cell cycle dependant transcription

Question 8

effect on growth factor receptors

Answer 8

increased/activation of growth factor receptors

Question 9

effect on growth factors themselves

Answer 9

increased growth factors

Question 10

effect on signalling

Answer 10

interference with intracellular signalling

Question 11

tumour supressor genes

Answer 11

normal cells which then undergoes a mutation event.

• inactivated tumour suppressor gene however there is NO effect of the mutation is only in one gene copy
• there is a second mutation event
• this then inactivates the second gene copy which then eliminates the tumour suppressor gene
• therefore stimulating cell survival and proliferation

Question 12

Rb acts as a gatekeeper, explain this theory

Answer 12

when active Rb prevents DNA synthesis
when phosphorylated it comes away from the DNA and allows expression of the S-phase genes so DNA synthesis can occur
HOWEVER
if a mutation occurs in the Rb then this is continuously inactive even when the cell doesn’t want to undergo proliferation. this is what leads to uncontrolled proliferation

Question 13

another class of tumour suppressor is the caretaker

Answer 13

these maintain the integrity of the genome by promoting DNA repair

• nucleoside excision repair
• mismatch repair
• DNA double strand break repair

Question 14

what can act as both a gate keeper and a care giver

Answer 14

p53 as it can stop and repair, or induce cell death

Question 15

what is the role of p53

Answer 15

when a mutation occurs it either:

• cell cycle arrest
• dna repair
• block of angiogenesis
• apoptosis

Question 16

tell me about VEGF

Answer 16

This is a protein which is produced when the cell becomes starved of oxygen and needs to undergo angiogenesis to create a semi stable (abnormal structure) mood supply

Question 17

steps to invasion of cells

Answer 17

tumour cells detach from each other become of reduced adhesiveness

• cells then attach to the BM via the laminin receptors
• cells secrete proteolytic enzymes, including type IV collagenase and plasminogen activator
• degradation of the BM and tumour migration follow

Question 18

what are the 7 deadly sins

Answer 18

• self-sufficiency in growth signals
• insensitivity to growth-inhibitory signals
• evasion of apoptosis
• defects in DNA repair
• limitless replicative potencial
• sustained angiogenesis
• ability to invade and metastasise