Flashcards in Neoplasia 2 Deck (65)
What would you target to control cell survival, growth and differentiation?
4 emerging hallmarks in cancer replication?
deregulating cellular energetics
4 classes of normal regulatory genes?
tumour suppressor genes
DNA repair genes
Example of DNA repair genes defective?
how would aberrant DNA repair lead to cancer?
rapid accumulation of mutations in 'hotspot' oncogenes/TSGs
Her2-neu, Ras, Myc are examples of?
P53, Rb, APC, PTEN are examples of?
How many alleles need to be lost to lose TSG function?
How many alleles of oncogenes need to be activated/mutated?
Types of gene mutations in cancer? 4 types
errors in DNA repair
point mutations in onco/TSGs
amplification of oncogenes
Difference between mutation and polymorphism?
mutation: any change away from what is defined as 'normal'
polymorphism: variation that is common in population (no sequence is 'normal')
Common amplifications/mutation in cancer?
What is RB gene mutation responsible for?
Common amplifications/mutation in cancer
oncogenes affect 5 categories of growth:
protein signal transduction
What is SNP in cancer?
single nucleotide polymorphism
polymorphisms in cancer depends how on SNPs?
how they are expressed, the alterations could change stability, influence risk
Oncogene amplification and overexpression are synonymous?
Nope. Amplification is more copies of a gene
What are double minutes in neoplasia?
extra chromosomes containing only oncogenes. holy shit.
Gene translocations and fusions make what?
novel hybrid genes that affect signaling pathway
BCR-ABL hybrid gene affects what?
What must you consider re: neoplastic growth?
rate at which tumor cells are shed or die or differentiate
what happens to the proportion of cells in growth fraction as it grows?
growth fraction declines
Example of high growth fraction tumours?
leukemias, lmphomas, small-cell carcinoa
example of low growth fraction tumours
low growth fraction tumours production vs. death are simliar? or different?
similar. production is 10% greater than loss
doubling time f clinically detectable colon or lung tumours is how long?
Pten blocks THIS important kinase
PI3 kinase (growth pathway)
What are proto-oncogenes?
normal cell proliferation genes
What are oncoproteins?
proteins that come from oncogenes
In oncogenesis, what happens with growth factors?
In oncogenesis, what happens with growth factor receptors?
In oncogenesis, what happens with cyclins/CDKs
uncontroled cell cycle progression
RAS Oncogenes (H-Ras & K-Ras), what happens in mutant RAS?
the negative feedback(GTP hydrolysis) of active RAS to inactive RAS is broken
What are P54 and RB?
TSGs that regulate cell cycle directly
Pten inhibits what?
oncogenic pathway of PI3 kinase
How do you get loss of heterozygosity in neoplasm?
Both TSG genes lost
how are familial predisposition and TSGs involved?
inherit one defective gene, lose the other one via mutation, or could lose both on an unlucky fluke
What the only cancer that only needs one gene mutation to activate?
prevalance of retinoblastoma?
treatment for retinoblastoma?
Rb causative factor only in eye?
Nope, features in many tumour types
define loss of heterozygosity (LOH)
loss of normal function of one allele where the other one was already inactivated.
What is Knudson's "two hit" hypothesis for LOH?
generation one has one RB allele gone, their kids all have one already gone so all it takes is another one to go before you get tumours
What is the guardian of the genome?
what is p53?
transcription factor that can regulate expression of cell cycle factors
p53 helps out a lot with what cellular response to damage?
What is miRNA?
microRNAs, non-coding single stranded that function as negative regulators of genes
about how many nucleotides are miRNA?
How would miRNA affect oncogenes?
not enough expressed leads to too much oncoproteins
How would miRNA affect TSGs?
too many miRNAs leads to too little tumour suppresor proteins
What does methylation around TSGs do?
epigenetic control of TSG expression is heritable?
pRB checkpoints which part of cell cycle?
end of G1
p53 checkpoints which part of cell cycle?
6 ways to evade apoptosis
1. reduce CD95
2. inactivate death signal via FLICE
3. upregulare BCL2
4. reduce BAX cause of loss of p53
5. loss of APAF-1
6. upregulation of apoptosis inhibitors
What happens with telomeres and cancer?
tumour cells reactivate telomerase and achieve immortality
4 steps for tumour to become metastatic:
1. detachment of cells from each other
2. degradation of ECM
3. attach to novel ECM areas
what cellular glues are disrupted in metastasis? 3 of them
are adherance molecules affected in cancer signalling pathways?
What are popular angiogenesis targets for therapeutics?
Explain tumour heterogeneity.
every tumour is different from it's primary tumour and every region within the same tumour can be different
what is a tumour initiating cell?
human tumour growing in mouse when transplanted
What are cancer stem cells?
arise from adult stem cells, intrinsic resistance to conventional therapies