Week 12 Flashcards
Cancer
A group of diseases that all involve abnormal cell grown that has the potential to invade or spread to other tissues
How does cancer occur?
A normal cell mutates and uncontrollably multiplies
Some mutations can be inherited that increase the risk of cancer
Loss of cell cycle control
Cell cycle checkpoints
Uses CDK complexes
G1 to S checkpoint: is the DNA damaged?
CDK binds to cyclin, phosphorylates proteins (to activate and inactivate) so they can move into S phase
Tumor-suppressor genes
Controls cell cycle control
Repairing DNA
Inactivated by mutations
Alleles act recessively
Rb gene
- Transcription repressor when unphosphylated, blocks transcription of genes required for S phase
- When phosphorylated, it is no longer blocking transcription
- Mutations act recessively
- Power to prevent S-phase
p53
Detects DNA damage
- Always produced and quickly degraded, phosphorylation stablizes, turns into active transcription factor and induces protein p21 expression (CDK inactivates), cell cycle arrests
- Can start apoptosis
What percent of cancers are associated with mutations in TP53?
50%
Oncogenes
Stimulate cell proliferation
ACTIVATED by mutations
Mutant alleles act dominantly*
Proto-oncogenes mutate into oncogenes
Driver mutations
Use cancer initiation and progression
- Can inactivate tumor suppressors/activate oncogenes, increases net cell growth
Passenger mutations
Don’t contribute to cancer
- Increased mutations due to driver mutations
- Majority of mutations found in mature cancers
Retinoblastoma
Cancer of the retina, dominant allele of Rb gene, 75% penetrance, requires two mutant alleles
Hereditary retinoblastoma
All cells have one mutant allele, one cell acquires the second somatic mutation
Why there is incomplete penetrance
Sporatic retinoblastoma
One cell acquires two somatic mutations
A lot lower chance of obtaining the second mutation
Mutations in telomerase
Can allow telomeres to be repaired and the cell to become immortal, results in chromosome instability
Ras protein
Mutations can allow it to signal growth even without growth factor
BRCA1 gene
Tumor suppressor gene that repairs DNA breaks
Frequency of germline mutation: 0.32%
Incidence of breast cancer: 90%
BRCA2
Tumor suppressor gene that repairs DNA breaks
Frequency of germline mutation: 0.69%
Incidence of breast cancer: 41%
Oncoviruses
Tumor-causing retroviruses
- Infect by using reverse-transcriptase to integrate RNA genome of virus into cell’s genome, becomes new components, budding, new virus
