Oncogenes and Tumour Suppressor Genes Flashcards
What are the six hallmarks of cancer?
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
What is gene amplification?
Production of multiple gene copies
What are chimeric genes?
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)
When can the formation of chimeric genes be a problem?
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
What is the Philadelphia Chromosome?
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
State some important oncogenes in human cancers.
SRC – tyrosine kinase Myc – transcription factor JUN – transcription factor Ha-Ras – membrane bound GTPase Ki-Ras – membrane bound GTPase
What is an example of an inherited cancer?
Retinoblastoma – malignant cancer of the developing retinal cells
What mutation causes retinoblastoma?
RB1 gene
13q14
What are the functional classes of tumour suppressor genes?
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
State some important tumour suppressor genes in human cancers
P53 – cell cycle regulator
BRCA1 – cell cycle regulator
PTEN – tyrosine and lipid phosphatase
APC – cell signalling
In what form is p53 inactive?
When it is bound to MDM2
What is p53 important for?
It is important for regulation of p53 target genes (involved in DNA repair, growth arrest, senescence etc.) and protein-protein interactions (e.g. apoptosis)
What is odd about p53 considering it is a tumour suppressor gene?
It acts in a DOMINANT manner –mutation of a single copy is sufficient to achieve dysregulation of activity
What deletion causes loss of the APC gene?
5q21
What is APC involved in?
Cell adhesion
Cell signalling
What is the risk of people with this mutation developing colon cancer?
90%
What signalling pathway is APC involved in?
WNT signalling
What is the main role of APC that prevents uncontrolled growth?
It breaks down beta-catenin so that it doesn’t bind to LEF1 and promote uncontrolled proliferation
Describe the step-by-step development of colorectal cancer.
APC mutations –> hyperproliferative epithelium
DNA hypomethylation + K-ras mutation will make the polyps –> adenomas
P53 mutation will result in the development of carcinoma
How many copies of tumour suppressor genes do cells have
2
So normally mutation or deletion of 1 isn’t enough to promote cancer
Difference between activity of oncogenes and tumour suppressor genes
Oncogenes are active in tumours but tumour suppressor genes inactive
Types of mutations in oncogenes
Translocations or point mutations
Mutations associated with tumour suppressor genes
Deletions
Difference in hereditary nature of mutations in oncogenes and tumour suppressor genes
Tumour suppressor genes can actually be inherited
Do oncogenes and tumour suppressor genes tend to be recessive or dominant
Oncogenes- dominant
Tumour suppressor- recessive
Specificity of oncogenes and tumour suprressor genes
Broad tissue specificity in oncogenes
Specificity of tumour suppressor genes
Very tissue specific
Tumours associated with oncogenes and tumour suppressor genes
Oncogenes- leukaemia and lymphoma
Tumour suppressor- solid tumours
