oncogenes

Question 1

how many genes are associated with germline mutations and somatic mutations?

Answer 1

70 germline and 342 somatic

Question 2

what is a point mutation

Answer 2

the substitution of one base pair of a DNA sequence by another e.g. C-G is replaced by A-T

Question 3

missense mutation

Answer 3

when there is a substitution which results in a different amino acid and a change in protein function

Question 4

what happens if the point mutation is at a splice junction site

Answer 4

correct splicing doesnt happen and whole exon is missed out

Question 5

translocation mutation

Answer 5

part of one chromosome is joined to another

Question 6

how to detect translocation mutation

Answer 6

karyotypic (cytogenetic) analysis of tumour cells

Question 7

what does gene amplification do to levels of mRNA transcribed from the gene

Answer 7

increases them, leading to increase in proteins

Question 8

oncogene families (4)

Answer 8

growth factors, growth factor receptors, signal transduction proteins and nuclear regulatory proteins

Question 9

type of growth factor receptors

Answer 9

Receptor tyrosine kinases

Question 10

2 types of signal transduction proteins

Answer 10

protein tyrosine kinases and secondary signalling molecules

Question 11

2 types of nuclear regulatory proteins

Answer 11

transcription factors and cell cycle proteins

Question 12

what is RAS

Answer 12

small GTPase

Question 13

what do the RAS genes encode

Answer 13

21-kDa guanine nucleotide binding proteins that locate at the surface of the cell membrane via lipid tail

Question 14

what does RAS do

Answer 14

regulates length of time a signal is transduced from its upstream RTK

Question 15

what is an RTK

Answer 15

receptor tyrosine kinase

Question 16

what is a receptor tyrosine kinase

Answer 16

transmembrane receptor with cytoplasmic domains which act as tyrosine kinases when extracellular ligand is bound

Question 17

when is the RAS protein activated

Answer 17

when a growth factor binds to its receptor

Question 18

what happens when RAS is activated

Answer 18

it causes a cascade of intracellular phosphorylation which ends up activating a transcription factor, this makes CDKs and cyclins so the cell can go from G1-S phase

Question 19

what happens when you have a mutated RAS gene

Answer 19

the RAS proteins on the cells membrane are already activated so the cascade of phosphorylation is always happening so there is an overproduction of CDKs and cyclins

Question 20

what do MYC genes code for

Answer 20

proteins used for cell growth, survival and activity

Question 21

what happens when the MYC gene is mutated

Answer 21

more cell growth, survival and activity. A cell can bypass the checkpoints in the cell cycle

Question 22

what do oncogenes encode

Answer 22

oncoproteins - don’t need GFs to grow

Question 23

how are the proteins encoded by ras genes activated

Answer 23

missense point mutations at 3 amino acids

Question 24

how is Ras regulated

Answer 24

after p21 is formed a GTPase activating protein p120 associates with Ras-GTP, stimulating p21 GTPase activity

Question 25

how does neurofibromin deactivate ras

Answer 25

it removes a phosphate

Question 26

the problem of ras regulation in cancer

Answer 26

there are activating mutations at G12,G13 and Q61 which result in conformational changes to p21 so it does not interact with p120 as much. mutant ras then remains active

Question 27

what does GAP mean

Answer 27

GTPase activating protein

Question 28

what is required for ras-dependent transformation

Answer 28

functional Rho proteins

Question 29

5 Ras directed therapies

Answer 29

1. antisense oglionucleotides
2. antisense RNA
3. antisense ribozymes
4. farnesyl transferase inhibitors
5. immunisation against ras oncoproteins

Question 30

what are antisense oglios/RNA/RNAi

Answer 30

small pieces of DNA/RNA which inhibit gene expression by acting on pre-mRNA or RNA targets

Question 31

what are antisense oglios/RNA/RNAi advantages

Answer 31

ease of production, good heteroduplex formation

Question 32

what are antisense oglios/RNA/RNAi disadvantages

Answer 32

rapidly degraded, delivery problems, large repeat doses needed

Question 33

how are virus’ used against ras

Answer 33

they exploit ras pathways , activated ras allows for virus replication

Question 34

farnesyl transferase inhibitors against ras

Answer 34

ras needs an attachment to the plasma membrane via a farnesyl group to the cystine of the carboxyterminal by farnesyl transferase

Question 35

what happens if Kras or Nras is mutated

Answer 35

cancer is not responsive to ras targeted therapy