L05: Oncogenes

Question 1

What is an oncogene

Answer 1

A gene that has the potential to cause cancer when mutated or overexpressed

Question 2

What are oncogenes derived from

Answer 2

Proto-oncogene

Question 3

What is a proto-oncogenes

Answer 3

Normal cellular gene that opromotes normal cell growth and proliferation in a regulated matter

Question 4

How does a photo-oncogene become a oncogene

Answer 4

Gene mutation

Question 5

What are the products of oncogenes

Answer 5

Growth factor receptors
Signal transuction molecules
Transcription factors

Question 6

For a proto-oncogene to become an oncogene how many alleles need to be mutated

Answer 6

One allele (dominant allele)

Question 7

Can oncogenes become involved in the hallmarks of cancer

Answer 7

Yes

Question 8

What are the 4 ways in which oncogenes become activated

Answer 8

1) point mutations introduced to the gene
2) amplification of gene that includes proto-oncogene
3) chromosome translocation that brings proto-oncogene under the control of a different promoter
4) chromosome translocation that brings 2 genes together

Question 9

What does point mutation to a a gene result in

Answer 9

Altering the characteristic of a protein

Question 10

What does amplification of a gene that includes proto-oncogene lead to

Answer 10

Overexpression of a gene products

Question 11

What does chromosome translocation that brings proto-oncogene under the control of a promoter lead to

Answer 11

Protein expression

Question 12

What does translocation that brings 2 genes together result in

Answer 12

A protein with novel characteristics

Question 13

In a normal cell what happens to DNA

Answer 13

Transcribed into RNA

Question 14

In a cell what happens to RNA

Answer 14

Translated into protein

Question 15

Name an example of a gene that undergoes point mutation which alters characteristic of the protein

Answer 15

RAS

Question 16

Which 3 genes encode for RAS

Answer 16

KRAS
NRAS
HRAS

Question 17

If there is a point mutation for RAS what happens to RAS

Answer 17

Permanently switched on

Question 18

What is the role of activated RAS

Answer 18

Pass on the signal from a tyrosine kinase receptor for gene expression

Question 19

What are the 3 amino acids of RAS

Answer 19

G12
G13
Q61

Question 20

If there is a mutation of the RAS gene how many amino acids are mainly affected

Answer 20

1 out of the 3

Question 21

What causes the activation of a normal ras protein

Answer 21

Converting GDP (found in inactive RAS) to GTP

Question 22

How does the mutations of RAS allow it to become acitvated

Answer 22

It changes the amino acids and therefore the binding of GTP

Question 23

Normally what removes GTP from ras to switch it off

Answer 23

GAP

Question 24

If there is an oncogenic RAS mutation what happens to GAP

Answer 24

GAP becomes blocked

Question 25

Apart from directly giving mutation to the RAS gene what are the other ways of activating RAS permanently

Answer 25

Mutating the RTK (receptor tyrosine kinase) permanently so it signals to RAS permanently

Question 26

Name an exmaple of a RTK that causes the permanent activation of itself and RAS

Answer 26

Egfr

Question 27

Name 2 examples of amplification of piece of gene that includes a proto-oncogene

Answer 27

MYCN | EGFR

Question 28

What type of cancer is MYCN amplification most common in

Answer 28

Neuroblastoma

Question 29

In a normal cell how many copies of MYCN are there

Answer 29

2

Question 30

What are the 2 ways of amplification MYCN

Answer 30

1) many copies of MYCN (more than 2) become present on normal chromosome and extra chromosomal 2) MYCN has multiple copies on a single chromosome

Question 31

What does amplification of MYCN lead to

Answer 31

Overexpression of MYCN protein

Question 32

Name 2 examples of where chromosome translocation bring proto-oncogene under the control of a promoter

Answer 32

C-MYC | BCL-2

Question 33

What type of cancer is c-MYC a hallmark of

Answer 33

Burkitt lymphoma

Question 34

Which chromosome is the translocation of c-MYC found on in burkitt lymphoma

Answer 34

Chromosome 8 and 1 immunoglobulin loci

Question 35

What leads to c-MYC expression

Answer 35

IGH enhancer

Question 36

What does too much c-MYC lead to

Answer 36

Cell growth Proliferation Ribosomal synthesis Protein synthesis

Question 37

Which cancer is BCL-2 involved in

Answer 37

Follicular lymphoma

Question 38

What does translocation occur between

Answer 38

Chromosome 18 and iGH on chromosome 14

Question 39

What is BCL2

Answer 39

A pro survival gene that counteracts apoptosis

Question 40

Name an example of when a chronometer translocation brings 2 genes together

Answer 40

BCR-ABL

Question 41

What cancer is BCR-ABL found in

Answer 41

Chronic myeloid leukemia

Question 42

Between what 2 chromosome does translocation occur

Answer 42

22 and 9

Question 43

What does BCR-ABL lead to

Answer 43

Increased cell survival | Increased proliferation

Question 44

What medicine can block the fusion of BCR-ABL

Answer 44

Imatinib

Question 45

What is the role of imatinib

Answer 45

Inhibits tyrosine kinase by prevent ATP binding

Question 46

What causes the activation of tyrosine kinase receptors EGFR

Answer 46

Phosphorylation of tyrosine resides

Question 47

How do tyrosine residues become activated

Answer 47

When ATP bind to the packed in tyrosine kinase receptor

Question 48

How can we block the acitvation of Tyrosine kinase receptors so

Answer 48

Tyrosine kinase receptors

Question 49

Name a first generation tyrosine kinase inhibitor

Answer 49

Gefitinib

Question 50

How does gefitinib work

Answer 50

Prevent ATP binding by competing with ATP

Question 51

What is a risk of using 1st generation tyrosine kinase inhibits

Answer 51

Drugs resistance

Question 52

If we get drug resistance what is the other option of treatmetn

Answer 52

Using 2nd generation tyrosine kinase inhibitor

Question 53

Name an example of a second generation TKI

Answer 53

Afatinib

Question 54

How does afatinib work

Answer 54

Irreversible binding to atp pocket in the tyrosine kinase receptor

Question 55

Name an example of a 3rd generation TKI

Answer 55

Asimertinib

Question 56

What is the role of asimertinib

Answer 56

Bind to mutated EGFR that have become drug resistant

Question 57

What are the ways we can target EGFR/RAS/MAPK pathway

Answer 57

Target the proteins within the pathway

Question 58

Name a drug that is used to target RAF

Answer 58

Vermurafenib | Dabrafenib

Question 59

Name a drug that is used to target MEK protein

Answer 59

Trametinib