Lecture 27

Question 1

Leukocoria

Answer 1

A white reflex of the eye, so when using film cameras instead of having red eyes (reflecting BVs) its white, reflecting a tumor, retinoblastoma

Question 2

Retinoblastoma

Answer 2

Often hereditary since if comes from the loss of function of a tumour suppressor gene, if its not hereditary its still the same disease
Could be unilateral or bilateral, one or both eyes

Question 3

What’s the two hit hypothesis abt retinoblastoma

Answer 3

Idea that for kids to develop unilateral retinoblastoma (without the genetic factor) it took 2 hits, 2 specific mutations to render both copies of the Rb gene non functional

Question 4

Why do some kids develop unilateral and others bilateral retinoblastoma

Answer 4

Bilateral had the tendency to be genetic, so both eyes wouldve had 1 or both copies rendered dysfunctional from the get go
Unilateral is usually not genetic because of the 2 hit hypothesis, both genes have to be specifically rendered non functional, not likely that it would occur in both eyes, not at similar times anyway

Question 5

Does inheriting a mutated tumor suppressor gene automatically mean you will develop cancer

Answer 5

No, not necessarily, its an increased susceptibility, its a question of penetrance (whether or not its expressed)

Question 6

How does Rb do its tumor suppressing function

Answer 6

It inhibits E2F, a TF that promotes transition to S phase, and it inhibits it to make sure the environment is right for division, and when the time and factors are right, cyclin D cdk will phosphorylate Rb to inhibit its blocking action, allowing S phase to occur
Without it, E2F is always on and we cant regulate the cell cycle, cant stop the growth it just keeps going

Question 7

When does p53 kick in

Answer 7

When theres DNA damage, receives distress signals from multiple people, its a TF that activates the transcription of genes involved in cell cycle arrest (allowing repair of DNA), can also incur senescence (permanent cell cycle arrest)
Without this fail safe cells not fit for division will divide, increasing genetic instability

Question 8

What are the most common p53 mutations

Answer 8

Mis-sense mutations in the DNA binding domain of the TF (one base pair replaced such that we get a new amino acid)

Question 9

Is p53 haplosufficient or haploinsufficient

Answer 9

P53 acts as a tetramer, so if even one of these is off we cant interact and perform proper function, so p53 is haploinsufficient because its a dominant negative mutation

Question 10

How can HPV viral oncoproteins affect tumor suppressor genes

Answer 10

Viral oncoproteins block or inhibit tumor suppressor genes like p53 or Rb
E6 (from virus) inhibits p53
E7 (from virus) inhibits Rb
Note that viruses arent trying to make tumors, theyre just trying to make more of themselves, and that involves a lot of growth so they inhibit the tumour suppressors

Question 11

Clonal evolution

Answer 11

Concept that one cell may get one advantageous mutation so that line will proliferate above all others, but then one cell from that cohort will get a beneficial mutation and again, thats the line that’ll be favored, and this repeats, basically the one with the most beneficial mutation wins out and we make more like it because its working so well