Lecture 32

Question 1

what is leukocoria?

Answer 1

a white reflex in pupil

Question 2

is sporadic retinoblastoma unilateral or bilateral?

Answer 2

unilateral

Question 3

what is the two-hit hypothesis in sporadic cases?

Answer 3

two hits must happen to 1 cell –> rare and takes longer to develop

Question 4

what is the two-hit hypothesis in inherited cases?

Answer 4

inherits 1 hit –> another hit must occur –> more common, can happen to more than one cell

Question 5

what does the two-hit hypothesis match?

Answer 5

two-hit hypothesis is consistent with the idea of having recessive mutations in both alleles of 1 gene

Question 6

are tumour suppressor mutations haplosufficient or haploinsufficient? why?

Answer 6

haplosufficient –> recessive so 1 WT allele is enough to give WT phenotype

Question 7

tumour suppressor genes are often inherited as a __________ gene

Answer 7

tumour suppressor genes are often inherited as a dominant trait

Question 8

what protein is the guardian of the G1/S checkpoint?

Answer 8

Rb

Question 8

describe how tumour suppressor genes are often inherited as a dominant trait

Answer 8

ppl born with 1 hit have a very high chance of acquiring 2nd hit

Question 8

normal role of Rb

Answer 8

binds E2F to keep it inactive, then releases with increasing [cyclin] to allow E2F to stimulate transcription of DNA replication genes

Question 8

what is known as the guardian of the genome?

Answer 8

p53

Question 9

what activates p53?

Answer 9

DNA damage

Question 9

what does p53 activity lead to? (3)

Answer 9

1. transient cell cycle arrest
2. senescence
3. apoptosis

Question 10

what proportion of human tumours have p53 mutation?

Answer 10

> 50%

Question 11

3 domains of p53

Answer 11

1. Transcription Activation Domain
2. DNA-Binding Domain
3. Oligomerization Domain

Question 12

what domain of p53 is mainly mutated?

Answer 12

DBD

Question 13

describe mutated p53

Answer 13

unable to bind DNA bc DBD mutated but OD is intact so can still form tetramer

Question 14

many p53 mutant alleles function as _________ _________

Answer 14

many p53 mutant alleles function as DOMINANT NEGATIVE

Question 15

what does p53 mutant do?

Answer 15

mutant p53 binds WT p53 to prevent it from acting at DNA

Question 16

what do viral oncogenes from DNA tumour viruses do?

Answer 16

bind and inactivate Rb and p53

Question 17

consequence of viral oncogenes from DNA tumour viruses inactivating Rb and p53

Answer 17

Rb –> express genes for DNA replication

p53 –> cell cycle continues, no apoptosis

Question 18

describe the clonal evolution of cancer cells (3 stages)

Answer 18

1. one cell acquires mutation that gives proliferative advantage, making clones of mutated cells
2. one of the clones may acquire 2ND mutation that gives additional proliferative advantage
3. eventually accumulate mutations to make fully transformed cancer cells

Question 19

describe the genetic changes in colon cancer development

Answer 19

A) lose APC tumor supressor
1. polyp forms
2. benign, precancerous tumour grows

B) activate Ras oncogene
1. adenoma (benign) forms

C) lose p53 tumor suppressor
1. carcinoma (malignant) forms

D) lose anti-metastasis gene
1. metastasis

Question 20

what happens when PD-1 is activated?

Answer 20

Tumor cells activate PD-1 to suppress T cells

Question 21

what is a major contributor to cancer development?

Answer 21

environmental factors