Basic cancer genetics

Question 1

hallmarks of cancer

Answer 1

ability to replicate indefinitely
ability to evade apoptosis

Question 2

key mutations that drive cancer

Answer 2

mutations that inactivate DNA repair pathways or that increase the rate of cell division and replication

Question 3

cancer stem cell

Answer 3

normal stem cell has a mutation affecting division or apoptosis
becomes a cancer cell that can self renew but has abnormal behaviour

Question 4

oncogenes

Answer 4

activation by somatic gain of function mutation in one copy of a gene >drive cancerous formation
associated cancers arise sporadically

Question 5

philadelphia chromosome and leukemia

Answer 5

Translocation between C9 and 22
Breakpoints in ABL and BCR genes
Fusion of part of BCR and part of ABL gene
ABL promotes proliferation when on but fusion of BCR locks it on causing uncontrolled proliferation that cannot be turned off

Question 6

MYCN amplification and neuroblastoma

Answer 6

Myc is a TF (acts as an oncogene) that interacts with Max and binds to promoter/ e box to drive proliferation
overactivation of e box>over proliferation

Question 7

tumour suppressor genes

Answer 7

biallelic inactivation via mutation leads to tumorigenesis
associated cancers can show family history or occur sporadically

Question 8

knudsons two-hit hypothesis for retinoblastoma

Answer 8

mutation in RB1 tumour suppressor gene
The first hit (mutation) in one allele still leaves the other functional.
The second hit knocks out the remaining functional copy, completely disabling the tumor suppressor function.

Question 9

breast cancer

Answer 9

BRAC1 BRAC2 encode proteins required for efficient repair of damaged DNA

Question 10

non homologous end joining as a DNA repair mechanism

Answer 10

sticks segments together but doesn’t account for the missing segment. Error prone

Question 11

homologous recombination as a DNA repair mechanism

Answer 11

error free, enzymes digest part of one of the strands on both. Search cell for sequence homology via strand invasion
Polymerase used as primer>extension. Fills in missing section

Question 12

BRAC1

Answer 12

recognises strand break, binds to break junction and recruits BRAC2 RAD51 complex to the single strand
RAD51 unloaded onto strand for strand invasion

Question 13

fanconis anaemia

Answer 13

congenital
associated with bone marrow failure and developmental abnormalities and increased leukemia risk
caused by biallelic mutations in any one of several genes including in BRAC2

Question 14

fanconis anaemia v breast cancer development

Answer 14

inherited from parents: one normal and one mutated BRAC2 leads to breast cancer if the other BRAC2 becomes mutated in adult breast
if 2 defective BRAC2 inherited>anaemia

Question 15

von hippel lindau syndrome

Answer 15

fatigue, poor motor coordination and vision impairment
one mutated copy of VHL gene
somatic inactivation of second VHL gene>tumours in vasculature

Question 16

VHL

Answer 16

interacts with HIF-a and tags it with ubiquitin for degradation
VHL defective means HIF-a binds other TFs and activated other genes like VEGF that drives angiogenesis