Oncogenes and Tumour Suppressor Genes

Question 1

What are the six hallmarks of cancer?

Answer 1

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

Question 2

What is gene amplification?

Answer 2

Production of multiple gene copies

Question 3

What are chimeric genes?

Answer 3

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)

Question 4

When can the formation of chimeric genes be a problem?

Answer 4

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

Question 5

What is the Philadelphia Chromosome?

Answer 5

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

Question 6

State some important oncogenes in human cancers.

Answer 6

SRC – tyrosine kinase  
Myc – transcription factor  
JUN – transcription factor 
Ha-Ras – membrane bound GTPase 
Ki-Ras – membrane bound GTPase

Question 7

What is an example of an inherited cancer?

Answer 7

Retinoblastoma – malignant cancer of the developing retinal cells

Question 8

What mutation causes retinoblastoma?

Answer 8

RB1 gene

13q14

Question 9

What are the functional classes of tumour suppressor genes?

Answer 9

Regulate cell proliferation  
Maintain cellular integrity  
Regulate cell growth  
Regulate the cell cycle  
Nuclear transcription factors  
DNA repair proteins  
Cell adhesion molecules  
Cell death regulators

Question 10

State some important tumour suppressor genes in human cancers

Answer 10

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

Question 11

In what form is p53 inactive?

Answer 11

When it is bound to MDM2

Question 12

What is p53 important for?

Answer 12

It is important for regulation of p53 target genes (involved in DNA repair, growth arrest, senescence etc.) and protein-protein interactions (e.g. apoptosis)

Question 13

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

Answer 13

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

Question 14

What deletion causes loss of the APC gene?

Answer 14

5q21

Question 15

What is APC involved in?

Answer 15

Cell adhesion

Cell signalling

Question 16

What is the risk of people with this mutation developing colon cancer?

Answer 16

90%

Question 17

What signalling pathway is APC involved in?

Answer 17

WNT signalling

Question 18

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

Answer 18

It breaks down beta-catenin so that it doesn’t bind to LEF1 and promote uncontrolled proliferation

Question 19

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

Answer 19

APC mutations –> hyperproliferative epithelium
DNA hypomethylation + K-ras mutation will make the polyps –> adenomas
P53 mutation will result in the development of carcinoma