oncogenes and TSG

Question 1

in general terms, what gives rise to cancerous cell behaviour?

Answer 1

mutations and epigenetic changes

Question 2

what is metastasis?

Answer 2

cancer cells invade surrounding tissues and remote organs

Question 3

what does evolution of a tumour depend on?

Answer 3

microenvironment provided by stromal cells

Question 4

what are the 2 cancer critical genes?

Answer 4

proto-oncogenes
tumour suppressor genes

Question 5

how do proto-oncogenes drive a cell towards cancer?

Answer 5

gain of function mutation

Question 6

how do TSG contribute towards cancer?

Answer 6

loss of function mutation

Question 7

what are pathways that are damaged in tumours?

Answer 7

p53 pathway
Rb pathway
RTK/Ras/PI3K

Question 8

what is p53 pathway responsible for?

Answer 8

regulates responses to stress and DNA damage

Question 9

what is the Rb pathway responsible for?

Answer 9

initiation of the cell division cycle

Question 10

what is the RTK/Ras/PI3K pathway responsible for?

Answer 10

signals for cell growth and division from outside cell in to the cell

Question 11

what is p53 protein function?

Answer 11

transcription factor

Question 12

what does p53 activation lead to?

Answer 12

cell cycle arrest (G1/G2)
senescence or apoptosis which prevent propagation of damaged DNA

Question 13

what causes Li-Fraumeni syndrome?

Answer 13

loss of function mutation in TP53

Question 14

what stage in the cell cycle do cells grow in prep for DNA replication?

Answer 14

G1

Question 15

how may the 1st copy of TSG be inactivated?

Answer 15

chromosomal deletion/ inactivated by point mutation

Question 16

how may the 2nd copy of TSG be lost?

Answer 16

errors in chromosome segregation, mitotic recombination, or gene conversion.

Question 17

what are epigenetic changes that can permanently inactivate a TSG?

Answer 17

methylation
DNA packaging

Question 18

how is p53 lost by targeted degradation?

Answer 18

HPV activates E3 enzyme
E3 enzyme ubiquitinates p53

Question 19

what is ubiquitin?

Answer 19

a protein TAG attached to a protein that targets it for degradation

Question 20

how is p53 lost by gene mutation?

Answer 20

monoallelic mutation may confer a dominant-negative function on TSG products

Question 21

what is retinoblastoma?

Answer 21

rare childhood tumour in the neural precursor cells of the retina

Question 22

how does retinoblastoma occur?

Answer 22

Deletions in chromosome 13
Rb gene which encodes Rb protein – a key suppressor of the cell cycle progression.

Question 23

what are oncogenes?

Answer 23

tumour promotors

Question 24

what are types of over activity?

Answer 24

deletion/ point mutation in coding sequence
mutation in regulatory region of gene
gene amplification
chromosome rearrangement

Question 25

what activates the PI3/ Akt/mTOR pathway?

Answer 25

insulin

Question 26

what does the PI3/Akt/mTOR do?

Answer 26

drives cancer cells to grow

Question 27

what suppresses the PI3/Akt/mTOR pathway?

Answer 27

PTEN phosphatase

Question 28

how may cancer cell genomes be obtained?

Answer 28

exome analysis

Question 29

what is exome analysis?

Answer 29

looks for mutations in the genes that code for protein sequence/ expression of gene.