Hereditary Cancers Flashcards
Characteristics of Cancer Cells
- hetergeneous
- usually result from multiple mutations
- cancer cells can have multiple lineages
Driver v Passenger Mutations
Driver mutations= directly affect cell cycle regulation, growth or apoptosis; lead to tumor formation
Passenger mutations= secondary effects of cancer development
Oncogenes
Dom inheritance (only need mutation in 1 allele)
- Proto-oncogenes normally regulate cell growth become mutated or overactive in expression –> oncogenes
- Results in gain of function
Tumor Suppressor Genes
Rec inheritance (need mutation in both alleles)
-These genes normally anti-proliferation genes
Double Hit Theory
If you inherit 1 mutated tumor suppressor gene then you have an inc likelihood of mutation in 2nd tumor suppressor gene –> 2 bad alleles
**Can happen as a result of loss of heterozygosity; recombination event in parents where the same allele copy (either mom or dad) ends up on both chromosomes
3 Molecules of Cell Cycle Checkpoints
1- cyclins (bind CDKs)
2- CDKs (kinases- phosphorylate downstream proteins on serine or threonine - phosphate either act or inactiv protein)
3- CDK Inhibitors (activated by tumor suppressor proteins to block cell cycle at given point by interacting w/ CDKs to inactivate them)
**ALL SPECIFIC
Rb
TSG whose inactivation –> retinoblastoma
- Kids either inherit 1 bad copy and then have 2nd mutated OR both sporadically inactivated by deletion or mutation
- Rb is ACTIVATED when phosphorylated
p53
TSG whose inactivation –> Li-Fraumeni Syndrome
-p53 is INACTIVATED when phosphorylated
Gatekeeper Tumor Suppressors v Caretaker Tumor Suppressors
Gate= genes whose products inhibit cell proliferation (normally suppress growth)
Care= genes responsible for maintaining integrity of genome and fidelity of info transferred to daughter cells (eg DNA repair genes)- if lose function –> inc frequency of DNA mutations in oncogenes and other TCGs
