L11 - Mutations And Cancer

Question 1

Mutations

Answer 1

• Responsible for diversity of genes found among organisms

- can have major, minor, positive or no effects on resulting protein structure and function

Question 2

Mutation locations

Answer 2

In body:
- germ line: passed on
- local/somatic: not whole body
In DNA:
- protein-coding region
- introns
- 5’/3’ UTR

Question 3

Types of mutations

Answer 3

• large scale alterations: chromosomal rearrangements

- small scale alterations: one or few nucleotides

Question 4

Types of small scale alterations

Answer 4

Substitution, indels

Question 5

Types of substitution mutation

Answer 5

Silent, mis-sense, nonsense

Question 6

Indels - 1 or 2 nts

Answer 6

Causes frameshift

Could lead to truncated protein

Question 7

Truncated protein

Answer 7

Shortened protein due to premature STOP codon

Question 8

Indels - 3 nt-pair

Answer 8

Maintained frameshift

Question 9

Wild-type beta-globin

Answer 9

5’ GAG 3’
- Glu - (acidic, -ve charge)
Normal hemoglobin
RBC: maximise surface area, flexible - can squeeze through tiny capillaries

Question 10

Sickle-cell beta-globin

Answer 10

5’ GUG 3’
- Val - (hydrophobic)
Sickle-cell hemoglobin
RBC is more rigid - can get clogged more easily in capillaries

Question 11

Sickle cell anaemia

Answer 11

• Missense substitution mutation

- result of accumulative effect: needs to happen to enough hemoglobins in RBC

Question 12

Importance of checkpoints

Answer 12

Appropriate molecular regulation of cell division critical for normal growth, development and maintenance

Question 13

Maturation promoting factor (MPF) function

Answer 13

phosphorylates many other proteins and allows mitosis to commence

Question 14

Maturation promoting factor (MPF) composition

Answer 14

Specific complex of cyclin and cyclin dependent kinase (CDK)

Question 15

Cyclin

Answer 15

• Protein fluctuating throughout cell cycle

- Many different forms - e.g cyclin D, E, A, B

Question 16

Cyclin dependent kinase (CDK)

Answer 16

• Kinase that is phosphorylated/activated when attached to cyclin
• Many types

Question 17

Stop and go signals

Answer 17

Gene products associated with checkpoints

Question 18

Go signals

Answer 18

Genes that normally stimulate cell proliferation

Question 19

Stop signals

Answer 19

Genes that normally keep proliferation in check (inhibition)

Question 20

If stop/go don’t work correctly due to mutation

Answer 20

Uncontrolled cell growth (cell escaped cell cycle control) and can result in tumours

Question 21

Cancer

Answer 21

Mutation in regulatory genes in somatic cells = uncontrolled cell division for that cell = can eventually lead to cancer

Question 22

Types of cancer-causing mutations

Answer 22

Genetic predisposition, acquired

Question 23

Genetic predisposition

Answer 23

In ALL CELLS of body

• inherited or de-novo
• issue/deficiency in a gene (typically one copy)
• doesn’t guarantee cancer but higher risk due to being further along path

Question 24

Acquired

Answer 24

Locally and initially in ONE CELL

- due to environmental mutagens (E.g UV damage, smoking, carcinogens, viruses, drugs, treatments)

Question 25

Go signal specific to cancer

Answer 25

Proto-oncogenes - mutation causes proto-oncogenes to become oncogenes = over-activation (render them constitutively active) = uncontrolled + accelerated cell growth

Question 26

Proto-oncogene examples

Answer 26

Ras (GTPase in G protein), Myc (transcription factor)

Question 27

Stop signals specific to cancer

Answer 27

Tumour suppressor genes - mutation causes deactivation (no longer function) = no inhibition of division of cells with damaged DNA = uncontrolled cell growth

Question 28

Examples of tumour suppressor genes

Answer 28

P53/TP53 (most common cancer-causing mutation, transcription factor), BRCA1/BRCA2 (associated with breast cancer + other cancer types)

Question 29

Pathway to cancer

Answer 29

Typically, multiple mutations (1-10) within the same cell are required for it to become fully cancerous

Question 30

Biopsy

Answer 30

Sample tumour itself to see possible cancer-causing mutations within - blood samples are not as useful for tumours/solid tumours

Question 31

Ras (proto-oncogene) normal function

Answer 31

1) ligand binds to receptor 2) Ras activated with ATP 3) protein kinases activated 4) transcription factor responds (activator) 5) protein that stimulates cell cycle produced (GO)

Question 32

Mutated Ras (oncogene) function

Answer 32

1) no ligand bound but Ras activated 2) DNA transcribed via signal transduction when it shouldn't 3) overexpression of GO protein

Question 33

P35 (tumour suppressor gene) normal function

Answer 33

1) DNA damaged (by UV light) 2) protein kinases activated 3) P35 transcription factor activated 4) protein that inhibits cell cycle made 5) damaged DNA not replicated

Question 34

Mutated P35 function

Answer 34

1) DNA damaged (by UV light) 2) protein kinases activated 3) P35 transcription factor NOT activated 4) inhibitory protein absent 5) damaged DNA replicated