21 - Carcinogenesis - molecular hallmarks

Question 1

carcinogens generally attack what

Answer 1

the tumour suppressor genes

Question 2

caretaker gene definition

Answer 2

maintain genetic stability by repairing damaged DNA and replication errors

Question 3

gatekeeper definition

Answer 3

play important roles in regulating normal growth

Question 4

negative regulator gatekeeper does

Answer 4

regulator of cell cycle and proliferation

Question 5

positive regulator gatekeeper

Answer 5

regulates apoptosis and cell differentiation

Question 6

carcinogens do what

Answer 6

induce molecular abnormalities in TSGs that cause reduced/lack of protein expression or inactivation i.e. loss of function

Question 7

inactivation of a TSG requires what

Answer 7

two hit hypothesis

Question 8

how can a TSG be activated according to the two hit hypothesis

Answer 8

lost during chromosomal non-disjunction

or gene conversion

or mitotic recombination

Question 9

retinoblastoma gene

Answer 9

RB1

Question 10

li-fraumeni gene

Answer 10

p53

Question 11

familial adenomatous polyposis gene

Answer 11

APC

Question 12

HNPCC gene

Answer 12

hMLH1, hMSH2

Question 13

which tumours are caretaker tumours

Answer 13

breast, ovarian

colon/endometrial

Question 14

proto-oncogenes

Answer 14

promote cell proliferation, survival, angiogenesis and negative regulation of apoptosis

Question 15

oncogenes

Answer 15

mutations lead to activated versions or increased expression of proto-oncogenes - GAIN of function`

Question 16

RAS - what is it

Answer 16

commonest oncoprotein

member of guanine nucleotide binding proteins called G-proteins

Question 17

RAS - problems

Answer 17

acquired a GTP molecule and shifted into an active state and unable to an inactive state.

Question 18

RB protein

Answer 18

retinoblastoma protein

Question 19

RB protein - what does it do?

Answer 19

non-proliferating cells behind here and suppresses activity.

may be epigenetically silenced

Question 20

immortal tumour cells

Answer 20

cells have a finite replicative life span as after numerous divisions they die due to loss of DNA from the telomeres. Tumours cells express telomerase that replaces this and they become immortal.

Question 21

TP53 involved with

Answer 21

apoptosis mainly

codes for transcription factor that induces transcription for >100 genes.

Question 22

most common genetic abnormality in human tumours

Answer 22

TP53 mutation

Question 23

TP53 mutation disease

Answer 23

Li-Fraumeni

Question 24

Angiogenesis in tumours

Answer 24

> 2mm require a good blood supply

VEGF induced by tumours - angiogenic factor.

Question 25

VEGF stands for

Answer 25

vascular endothelial growth factor

Question 26

E-cadherin

Answer 26

holds epithelial cells together

Question 27

tumours and E-cadherin

Answer 27

show loss of E-cadherin through mutation / hypermethylation of the gene… results in EMT

Question 28

what does EMT stand for

Answer 28

epithelial-mesenchymal transition

Question 29

Herceptin targets

Answer 29

targets HER2

Question 30

What does HER2 gene do?

Answer 30

codes for +ve growth factor receptor which is overexpressed in 30% of breast tumours