L05: Oncogenes Flashcards
What is an oncogene
A gene that has the potential to cause cancer when mutated or overexpressed
What are oncogenes derived from
Proto-oncogene
What is a proto-oncogenes
Normal cellular gene that opromotes normal cell growth and proliferation in a regulated matter
How does a photo-oncogene become a oncogene
Gene mutation
What are the products of oncogenes
Growth factor receptors
Signal transuction molecules
Transcription factors
For a proto-oncogene to become an oncogene how many alleles need to be mutated
One allele (dominant allele)
Can oncogenes become involved in the hallmarks of cancer
Yes
What are the 4 ways in which oncogenes become activated
1) point mutations introduced to the gene
2) amplification of gene that includes proto-oncogene
3) chromosome translocation that brings proto-oncogene under the control of a different promoter
4) chromosome translocation that brings 2 genes together
What does point mutation to a a gene result in
Altering the characteristic of a protein
What does amplification of a gene that includes proto-oncogene lead to
Overexpression of a gene products
What does chromosome translocation that brings proto-oncogene under the control of a promoter lead to
Protein expression
What does translocation that brings 2 genes together result in
A protein with novel characteristics
In a normal cell what happens to DNA
Transcribed into RNA
In a cell what happens to RNA
Translated into protein
Name an example of a gene that undergoes point mutation which alters characteristic of the protein
RAS
Which 3 genes encode for RAS
KRAS
NRAS
HRAS
If there is a point mutation for RAS what happens to RAS
Permanently switched on
What is the role of activated RAS
Pass on the signal from a tyrosine kinase receptor for gene expression
What are the 3 amino acids of RAS
G12
G13
Q61
If there is a mutation of the RAS gene how many amino acids are mainly affected
1 out of the 3
What causes the activation of a normal ras protein
Converting GDP (found in inactive RAS) to GTP
How does the mutations of RAS allow it to become acitvated
It changes the amino acids and therefore the binding of GTP
Normally what removes GTP from ras to switch it off
GAP
If there is an oncogenic RAS mutation what happens to GAP
GAP becomes blocked
Apart from directly giving mutation to the RAS gene what are the other ways of activating RAS permanently
Mutating the RTK (receptor tyrosine kinase) permanently so it signals to RAS permanently
Name an exmaple of a RTK that causes the permanent activation of itself and RAS
Egfr
Name 2 examples of amplification of piece of gene that includes a proto-oncogene
MYCN
EGFR
What type of cancer is MYCN amplification most common in
Neuroblastoma
In a normal cell how many copies of MYCN are there
2
What are the 2 ways of amplification MYCN
1) many copies of MYCN (more than 2) become present on normal chromosome and extra chromosomal
2) MYCN has multiple copies on a single chromosome
What does amplification of MYCN lead to
Overexpression of MYCN protein
Name 2 examples of where chromosome translocation bring proto-oncogene under the control of a promoter
C-MYC
BCL-2
What type of cancer is c-MYC a hallmark of
Burkitt lymphoma
Which chromosome is the translocation of c-MYC found on in burkitt lymphoma
Chromosome 8 and 1 immunoglobulin loci
What leads to c-MYC expression
IGH enhancer
What does too much c-MYC lead to
Cell growth
Proliferation
Ribosomal synthesis
Protein synthesis
Which cancer is BCL-2 involved in
Follicular lymphoma
What does translocation occur between
Chromosome 18 and iGH on chromosome 14
What is BCL2
A pro survival gene that counteracts apoptosis
Name an example of when a chronometer translocation brings 2 genes together
BCR-ABL
What cancer is BCR-ABL found in
Chronic myeloid leukemia
Between what 2 chromosome does translocation occur
22 and 9
What does BCR-ABL lead to
Increased cell survival
Increased proliferation
What medicine can block the fusion of BCR-ABL
Imatinib
What is the role of imatinib
Inhibits tyrosine kinase by prevent ATP binding
What causes the activation of tyrosine kinase receptors EGFR
Phosphorylation of tyrosine resides
How do tyrosine residues become activated
When ATP bind to the packed in tyrosine kinase receptor
How can we block the acitvation of Tyrosine kinase receptors so
Tyrosine kinase receptors
Name a first generation tyrosine kinase inhibitor
Gefitinib
How does gefitinib work
Prevent ATP binding by competing with ATP
What is a risk of using 1st generation tyrosine kinase inhibits
Drugs resistance
If we get drug resistance what is the other option of treatmetn
Using 2nd generation tyrosine kinase inhibitor
Name an example of a second generation TKI
Afatinib
How does afatinib work
Irreversible binding to atp pocket in the tyrosine kinase receptor
Name an example of a 3rd generation TKI
Asimertinib
What is the role of asimertinib
Bind to mutated EGFR that have become drug resistant
What are the ways we can target EGFR/RAS/MAPK pathway
Target the proteins within the pathway
Name a drug that is used to target RAF
Vermurafenib
Dabrafenib
Name a drug that is used to target MEK protein
Trametinib
