Lecture 32 Flashcards
what is leukocoria?
a white reflex in pupil
is sporadic retinoblastoma unilateral or bilateral?
unilateral
what is the two-hit hypothesis in sporadic cases?
two hits must happen to 1 cell –> rare and takes longer to develop
what is the two-hit hypothesis in inherited cases?
inherits 1 hit –> another hit must occur –> more common, can happen to more than one cell
what does the two-hit hypothesis match?
two-hit hypothesis is consistent with the idea of having recessive mutations in both alleles of 1 gene
are tumour suppressor mutations haplosufficient or haploinsufficient? why?
haplosufficient –> recessive so 1 WT allele is enough to give WT phenotype
tumour suppressor genes are often inherited as a __________ gene
tumour suppressor genes are often inherited as a dominant trait
what protein is the guardian of the G1/S checkpoint?
Rb
describe how tumour suppressor genes are often inherited as a dominant trait
ppl born with 1 hit have a very high chance of acquiring 2nd hit
normal role of Rb
binds E2F to keep it inactive, then releases with increasing [cyclin] to allow E2F to stimulate transcription of DNA replication genes
what is known as the guardian of the genome?
p53
what activates p53?
DNA damage
what does p53 activity lead to? (3)
- transient cell cycle arrest
- senescence
- apoptosis
what proportion of human tumours have p53 mutation?
> 50%
3 domains of p53
- Transcription Activation Domain
- DNA-Binding Domain
- Oligomerization Domain
what domain of p53 is mainly mutated?
DBD
describe mutated p53
unable to bind DNA bc DBD mutated but OD is intact so can still form tetramer
many p53 mutant alleles function as _________ _________
many p53 mutant alleles function as DOMINANT NEGATIVE
what does p53 mutant do?
mutant p53 binds WT p53 to prevent it from acting at DNA
what do viral oncogenes from DNA tumour viruses do?
bind and inactivate Rb and p53
consequence of viral oncogenes from DNA tumour viruses inactivating Rb and p53
Rb –> express genes for DNA replication
p53 –> cell cycle continues, no apoptosis
describe the clonal evolution of cancer cells (3 stages)
- one cell acquires mutation that gives proliferative advantage, making clones of mutated cells
- one of the clones may acquire 2ND mutation that gives additional proliferative advantage
- eventually accumulate mutations to make fully transformed cancer cells
describe the genetic changes in colon cancer development
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
what happens when PD-1 is activated?
Tumor cells activate PD-1 to suppress T cells
what is a major contributor to cancer development?
environmental factors
