Oncogenes and Tumour Suppressor Genes Flashcards Preview

Y2 Cancer (MCD) > Oncogenes and Tumour Suppressor Genes > Flashcards

Flashcards in Oncogenes and Tumour Suppressor Genes Deck (24)
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1
Q

What are the six hallmarks of cancer?

A
  • Disregard of signals to stop proliferating
  • Disregard of signals to differentiate
  • Capacity for sustained proliferation
  • Evasion of apoptosis
  • Ability to invade
  • Ability to promote angiogenesis
2
Q

What is gene amplification?

A

Production of multiple gene copies

3
Q

What are Chimaeric genes?

A

Genes that are formed by combinations of portions of one or more coding sequence to produce new genes (e.g. the swapping of tips of chromosomes)

4
Q

When can the formation of Chimaeric genes be a problem?

A

If one of the pieces of translocated DNA is a promoter, it could lead to upregulation of the other gene portion (this occurs in Burkitt’s lymphoma) If the fusion gene codes for an abnormal protein that promotes cancer

5
Q

What is the Philadelphia Chromosome?

A

Chromosome produced by the translocation of the ABL gene on chromosome 9 to the BCR gene on chromosome 22 The BCR-ABL fusion gene encodes a protein that promotes the development of cancer

6
Q

State some important oncogenes in human cancers.

A
  • SRC – tyrosine kinase
  • Myc – transcription factor
  • JUN – transcription factor
  • Ha-Ras – membrane bound GTPase
  • Ki-Ras – membrane bound GTPase
7
Q

What is an example of an inherited cancer?

A

Retinoblastoma – malignant cancer of the developing retinal cells

8
Q

What mutation causes retinoblastoma?

A

Due to mutation of the RB1 tumour suppressor gene on chromosome 13q14.

9
Q

State some important tumour suppressor genes in human cancers

A

P53 – cell cycle regulator BRCA1 – cell cycle regulator PTEN – tyrosine and lipid phosphatase APC – cell signalling

10
Q

In what form is p53 inactive?

A

When it is bound to MDM2

11
Q

What is p53 important for?

A

It is important for regulation of p53 target genes: DNA repair growth arrest senescence and important for protein-protein interactions such as apoptosis

12
Q

What is odd about p53 considering it is a tumour suppressor gene?

A

It acts in a DOMINANT manner –mutation of a single copy is sufficient to achieve dysregulation of activity

13
Q

What deletion causes loss of the APC gene?

A

5q21

14
Q

What is APC involved in?

A

Tumour supressor gene involved in: Cell adhesion Cell signalling

15
Q

What is the risk of people with a mutation causing loss of APC developing colon cancer?

A

90%

16
Q

What is the main role of APC that prevents uncontrolled growth?

A

APC protein helps control the activity of b-catenin in the WNT signalling pathway and thereby preventing uncontrolled growth.

17
Q

Describe the step-by-step development of colorectal cancer.

A
  1. APC mutations –> hyperproliferative epithelium
  2. DNA hypomethylation + K-ras mutation will make the polyps –> adenomas
  3. P53 mutation will result in the development of carcinoma
18
Q

What happens in each stage of the cell cycle?

A

G1:

  • Can enter G0 (senescent stage which can enter into G1 when prompted to)
  • Growth in mass
  • Centrosome duplication

S:

  • Chromosome duplication

G2:

  • Damage checks

M:

  • Mitosis and cytokinesis
19
Q

Where do checks occur in the cell cycle?

A

G1:

  • Restriction point to check for cell size and favourable environmental conditions
  • End check for DNA damage

G2:

  • Whole phase primarily dedicated to checking for damaged or unduplicated DNA and chromosomes
20
Q

What are the ways an oncogene can be activated?

A
  1. Mutation in the coding sequence e.g. point deletion that generates an abberantly active protein
  2. Gene amplification leading to over production of a normal protein
  3. Chromosomal translocation leading to chimaeric genes
  4. Insertional mutagens e.g. viral infections
21
Q

How can gene amplification occur?

A

Polymerase encounters an obstruction e.g. a molecule covalently bonded to the DNA then it backs up and repeats the same sequence.

Or insertion of a promoter gene to form and overexpressed chiameric gene

22
Q

How does normal Ras act as a proto-oncogene and how does abberant Ras cause cancer?

A

Normally:

  • Signal received via G protein to initiate cell proliferation
  • Adapter protein Grb2 activates Sos
  • Sos causes an exchange of GDP for GTP on Ras –> activate Ras
  • Ras then activates Raf - the first kinase in the ERK cascade (a cell proliferation pathway)
  • Raf-Ras complex activates GAP proteins
  • GAP proteins cleave GTP on RAS to GDP
  • This deactivates Ras causing Raf to unbind and stop signalling

Mutant Ras:

  • Fails to dephosphorylate GTP or Gap cant bind
  • Ras remains active.
  • Raf remains active
  • Constantly signals to proliferate
23
Q

In terms of activation, what is different between most proto-oncogenes and most TSG?

A

Proto-oncogenes require only 1 of the genes to become abberant for cancer to develop (dominant) TSG require both pairs of the gene to become abberant for cancer (recessive)

24
Q

How is p53 activated?

A

Many signals for MDM2 to unbind p53:

  • Hypoxia
  • Oncogene activation
  • DNA replicative stress
  • Telomere erosion
  • Ribonucleotide depltion etc

p53 is released and dimerises to act as a transcriptional factor or to interact with proteins involved in apoptosis