Biochemistry

Question 1

Karyotype

Answer 1

Question 2

Proto-oncogenes

Answer 2

Question 3

Tumour-suppressor genes

Answer 3

Question 4

p53 pathway

Answer 4

p53 blocks cancer progression by provoking transient or permanent growth arrest, by enabling DNA repair or by advancing cellular death programs.

Question 5

Rb pathway

Answer 5

Rb include tumor suppression, regulation of the cell cycle, differentiation, and apoptosis.

Question 6

RTK/Ras/PI3K pathway in cancer development

Answer 6

RTK - kinase that becomes hyperactive, persistently activating Ras.
Ras - protein that switches on cell growth
PI3K - stimulated by Ras (further pathways from this lead to increased cell survival and growth).

= tumour formation

Question 7

TP53

Answer 7

Gene that encodes p53.
In tumours TP53 gene was found to be deleted (i.e. p53 couldn’t be expressed).

Question 8

Li-Fraumeni syndrome

Answer 8

Loss of function mutations in TP53 (predisposed especially to breast cancer).

Question 9

Explain the mechanism that prevents cells being formed from damaged DNA?

Answer 9

1. p53 is phosphorylated so it can’t bind to Mdm2.
2. p53 accumulates at high levels stimulates production of p21.
3. p21 binds and inactivates key complexes arresting the cell in G1 (the first phase of the cell cycle before replication).

Question 10

How could tumour suppressor genes become inactivated?

Answer 10

1. Chromosomal deletion or inactivation by point mutation.
2. Epigenetic changes - permanently inactivate (methylation or DNA packing)

Question 11

How does HPV lead to cancer through targeted degradation?

Answer 11

E6 proteins target E3 ubiquitin ligase to p53, resulting in the transfer of ubiquitin peptides marks p53 for destruction.

Question 12

The activation of E3 enzyme is observed in more than __% of cervical carcinomas.

Answer 12

90

Question 13

Ubiquitin

Answer 13

a small protein that marks other proteins for degradation or cellular processes through E1, E2, & E3 genes.

Question 14

Loss of p53 by monoallelic mutation

Answer 14

Monoallelic mutation; one allele of the tumour suppressor gene is mutated.

Dominant-negative effects (good allele is dominated by bad, mutated allele)

Question 15

Retinoblastoma

Answer 15

Eye tumour in kids, allowed discovery of Rb gene

Question 16

Oncogenes

Answer 16

altered genes that have the potential to cause cancer by promoting abnormal cell growth and proliferation.

Question 17

Types of over activity: deletion or point mutation in coding sequence

Answer 17

Normal amounts of hyperactive protein

Question 18

Types of over activity: mutation in the regulatory region of the gene

Answer 18

normal protein overproduced

Question 19

Types of over activity: gene amplification

Answer 19

normal protein greatly overproduced

Question 20

Types of over activity: chromosome rearrangement

Answer 20

normal protein overproduced or alters the protein coding region causing transcribed gene —> hyperactive protein

Question 21

EGFR pathway in head and neck cancers.

Answer 21

1. contributes to cell growth, proliferation & survival
2. Overexpression or mutation of EGFR can cause tumour growth

Inhibitors used in cancer treatment !!