Block 3 Lecture 1 -- Cancer Overview Flashcards
What is transition mutation?
substitute purine for purine
What are the purine nucleotides?
A, G (2 rings)
What is a transversion mutation?
Substitute purine for pyrimidine or vice versa
What are the single base mutations?
1) transition
2) transversion
3) insertion
Define carcinogenesis:
the steps by which a normal cell is transformed into a cancer cell
What are the steps in carcinogenesis?
1) initiation
2) promotion
3) progression
What are cis-regulatory elements?
non-coding regions of DNA that regulate transcription
What are trans-acting factors?
transcription factors that bind cis-regulatory elements
Intron or exon…which is translated?
exon
What is a mutagen?
substance that causes an alteration to DNA sequence
What are the mutagenic products of UV light?
1) TT cyclobutane pyrimidine dimers
2) TC (6-4) pyrimidine-pyrimidone photoproducts
What is the signature mutation of TC (6-4) pyrmidine-pyrimidone products?
CC to TT transition
What forms of UV are most carcinogenic?
UVA and UVB
Where are nitrosamines found?
pickled foods
Where are polycyclic aromatic amines found?
large # found in tobacco smoke
What pathogens can be carcinogenic?
1) Kaposi’s sarcoma-associated herpesvirus
2) HBV
3) H. pylori
What are the types of mutations that may occur?
1) single base
2) deletion
3) translocations
What is an enhancer?
a cis-regulatory element that recruits proteins to initiate specific gene transcription
What is present in the 5’ un-translated region (UTR)?
1) high GC content – hairpin loops
2) cis-reg elements
3) Kozak initiation sequence
What are the types of DNA repair?
1) NER
2) BER
3) mismatch
4) recombinational
5) one-step repair
What is one-step DNA repair?
aka direct DNA repair
- reversal of base methylation
- O6-alkylguanine-DNA-alkyltransferase sacrifices self to transfer methyl/ethyl to own Cys residue
When is nucleotide excision repair used?
when damage generates a bulky, helix-distorting mutation
– UV damage
How are DNA/RNA tumor viruses carcinogenic?
encode proteins that block host cell tumor suppressor genes
What molecules are known carcinogens?
1) polycyclic aromatic amines
2) nitrosamines
How are polycyclic aromatic amines mutagenic?
- generate cascade of metabolic epoxides
- - epoxides near the “bay region” between aromatic rings are genotoxic
What type of cancer are nitrosamines linked to?
gastric
How are nitrosamines carcinogenic?
alkylnitrosureas form oxygen adduct on guanine residues
What is present in the 3’ untranslated region?
AAUAAA signal
– directs addition of Poly-A tail for stability
miRNA binding sites
What is haploinsufficiency?
single gene doesn’t express enough protein for wild-type phenotype
– can be result of 1 allele mutation of a tumor suppressor gene
What characteristics of electromagnetic radiation = higher energy?
higher frequency
shorter wavelength
What endogenous reactions generate mutations?
1) oxidative respiration (ROS)
2) lipid peroxidation (ROS)
3) spontaneous glycosidic bond hydrolysis (abasic site)
How does generation of an abasic site lead to mutations?
1) deamination of C to U
- - errors in replication, recombination
What are the main six hallmarks of cancer?
1) growth signal autonomy
2) evasion of growth inhibitory signals
3) evasion of apoptosis
4) angiogenesis
5) unlimited replicative potential
6) invasion and metastasis
What are the other 4 hallmarks of cancer?
1) genome instability and mutation
2) reprogramming energy metabolism
3) tumor-promoting inflammation
4) avoiding immune destruction
What determines normal replicative potential?
defined number of doublings before sensescence
– telomere length = Hayflick’s limits
How do cancer cells have unlimited replicative potential?
maintain telomere length
How does inflammation promote tumors?
generate ROS
How is energy metabolism re-programmed in cancer?
glycolysis even in presence of O2 due to high fuel and precursor demand
How are growth inhibitory signals evaded in cancer?
acquired mutation or gene silencing
What factors determine carcinogenesis in an individual?
1) net cell number
- - cell proliferation, differentiation, death
2) environmenet
3) reproductive life
4) diet
5) smoking
