Oncogenes

Question 1

What % of human genome can be translated

Answer 1

10%

Question 2

What do genes consist of?

Answer 2

Protein-coding exons and non-coding introns

Question 3

What are proto-oncogenes

Answer 3

Unmutated counterparts of oncogenes

Question 4

How many proto-oncogenes are associated with:

• Germ line mutations
• Somatic mutations

Answer 4

Germ line: 70

Somatic: 342

Question 5

What are the 2 basic classes of genes that lead to cancer?

Answer 5

Proto-oncogenes and tumour suppressor genes

Question 6

What is different about germ line mutations? (as opposed to somatic)

Answer 6

Germ line mutations can be inherited from one generation to the next (eg APC and P53)

Question 7

Which hallmarks of cancer are involved in oncogenes?

Answer 7

Genomic instability

Tumour promoting inflammation

Question 8

What are the 10 hallmarks of cancer

Answer 8

1. Self sufficiency in growth signals
2. Insensitivity to antigrowth/ growth inhibitory signals
3. Evasion of apoptosis
4. Limitless replicative potential
5. Sustained angiogenesis
6. Ability to invade and metastasize
7. Reprogramming energy metabolism
8. Evasion of immune system
9. Genomic instability
10. Tumour promoting inflammation

Question 9

What causes the change from proto-oncogene to oncogene?

Answer 9

Mutations of the proto-oncogene

Question 10

What are the 4 types of mutations?

Answer 10

Point mutation
translocation
gene amplification
deletion

Question 11

What is a point mutation?

Answer 11

Substitution of one base pair of a DNA sequence by another. May have effects depending on its position

Question 12

What is a missense mutation?

Answer 12

Type of point mutation where one amino acid is substituted for another, resulting in identical protein to wild type apart from one AA change

Question 13

What is a stop codon nonsense mutation?

Answer 13

Type of point mutation where mutated sequence encodes a signal for termination of translation (stop codon).
Results in truncated protein due to early termination

Question 14

What happens if a point mutation occurs in splice junction site?

Answer 14

Correct splicing events may not take place, whole exon may be missed out of mRNA

Question 15

What is a translocation mutation?

Answer 15

Part of one chromosome is joined to another, resulting in hybrid chromosome

Question 16

How are translocation mutations detected?

Answer 16

Karyotypic analysis (chromosome mapping) of tumour cells detects translocated genes

Question 17

What is gene amplification?

Answer 17

One copy of a gene multiplied thousands of times

Question 18

How does gene amplification contribute to oncogenesis?

Answer 18

Increases levels of mRNA transcribed from genes, therefor increasing levels of protein encoded by amplified gene.

Question 19

What is deletion?

Answer 19

Deletion of a single base pair.

Question 20

What are the effects of a deletion mutation?

Answer 20

Can cause frame shift or accidentally code for a stop codon (truncated protein)

Question 21

What is the difference between proteins and oncoproteins?

Answer 21

Oncoproteins do not require a growth factor, resulting in increased proliferation and malignant growth

Question 22

What does protein does RAS encode and what is the protein involved in?

Answer 22

RAS encodes GTP-binding protein which is involved in growth signaling pathway.

Question 23

What proteins can be oncogenes?

Answer 23

Growth factors (/ growth factor receptors)
Signal transduction proteins (eg protein tyrosine kinases)
Nuclear regulatory proteins (eg transcription factors, cell cycle proteins etc)

Question 24

Describe how a normal cell would respond to a growth factor?

Answer 24

GFs activated by stimuli, and bind to GF receptors.
Activates RAS by converting GDP to GTP
Transmit signal to kinases which transmit signal to nucleus
Activate transcription factors which begin cell cycle

Question 25

What are the 3 RAS genes?

Answer 25

H-ras, K-ras, N-ras

Question 26

What type of mutation activates proteins encoded by genes of RAS family?

Answer 26

Missense point mutations

Question 27

What do RAS genes encode?

Answer 27

21-kDa guanine nucleotide-binding proteins

AKA p21ras

Question 28

What does RAS do?

Answer 28

Regulates length of time a signal is transducer from its upstream RTK

Question 29

What is Sos? What is it involved with?

Answer 29

Sos is an exchange factor

It is involved with the conversion of GDP->GTP

Question 30

What regulates RAS?

Answer 30

Cycle:

• formation of p21ras.GTP (active ras)
• Neurofibromin (GTPase activating protein) associates
• Stimulation of p21 GTPase activity, -> inactive ras

Question 31

What happens if there is mutation in p21ras?

Answer 31

Reduce interaction, therefore GTP RAS cannot be converted back to GDP.
> cells continuously divide as increase activation of RAS pathway. (Cannot be inhibited)

Question 32

What are rho and rac?

Answer 32

Cytoskeleton architectural proteins

Question 33

What are antisense oligos?

Answer 33

Small pieces of DNA/RNA (~ 8-50bps) which inhibit gene expression by blocking transcription of molecules downstream

Question 34

What are the pros and cons to using antisense oligos?

Answer 34

+ easy production

• rapidly degraded by endonucelases
• problems with delivery
• large repeat doses required

Question 35

How is reovirus therapy used to kill cancer cells?

Answer 35

Virus exploits RAS pathway and only targets cancer cells.