(lecture 2) Flashcards
How do tumors arise? by accumulation of what?
somatic mutations
(Accumulation of Mutations in Cancer)
- contribution from non-tobacco mutagens in the environment is probably small
- Contributions from what are probably more important?
- What may be most important?
- crummy polymerases and errors during DNA repair
- errors by high fidelity enzymes during normal replication
(Gene Mutation Model)
(Oncogenes and Tumor Suppressor Genes)
- tumor suppressor genes do what or what?
- oncogenes promote what?
- Do all genes/proteins involved in growth regulation have oncogenic or tumor suppressive capacity?
- inhibit growth or promote apoptosis (two hits - knudson hypothesis)
- growth and survival (one hit)
- no
(The “Mutator” Hypothesis)
(Larry Loeb)
- Assumes that most heritable (and many sporadic) cancers are associated with changes in genes that control what?
- Most atypical polymerases have low fidelity and can lead to what?
- If the genotype is carried in the germline, it will increase the rate of mutation until what occurs?
- DNA repair (or synthesis)
- DNA duplication with essential errors
- essential genes that cause transformation are enabled or disabled
(Heritable Cancers vs. Sporadic Cancers)
- Sporadic cancers account for what percent of all cancers (in people)?
- Do both have a genetic component?
- 95%
- yes (sporadic cancers in the sense that they means that they have an effect on genes - not that they are inhertied)
(these slides have nothing to do with pictures)
(Heritable Cancers)
- manifest earlier or later?
- multiple or single tumors most of the time?
- how is long term survival?
- Associated with how many genes?
- variable penetrance
- lifetime risk can be as high as what?
- earlier (but after reproductive age)
- multiple
- poor (most often)
- single gene (~2-dozen syndromes identified in people)
- 9/10
only takes this allele to be inactivated in a single cell for there to be an effect
chances are likely that this will happen to someone who carries this genotype - so even though inhertied recessively - it has dominant phenotype
(Heritable Traits and Sporadic Cancers)
Heritable traits contribute to cancer risk
1-3. “risk” may take what three forms?
- susceptibility to transformation
- tumor behavior
- response to therapy (if you try to give collie convential chemotherapy won’t work cause its pump in brain is messed up to a mutation in the MRD gene)
- if you look at all dogs getting lymphoma - about 70% get b-cell and 30% get T-cell
- this shows that what kind of cancer the dogs developed had some kind of genetic basis
(cancers only arise in somatic cells - can’t be passed on in germ cells cause these cells owld be rendered dysfunctional)
(Epigenetics)
- epigenetic influence on gene expression (changes in methylation or acetylation) usually occur dut to malfunction of what?
- in many cases, tumors underexpress their genomes due to what?
- associated enzymes
- hypermethylation
(imprinting - when one set of genes turn off - an example of an epigenetic change)
(Sporadic Cancers)
- can manifest at any age, but usually strike when?
- usually how many tumors?
- survival?
- accumulation of what?
- is there any penetrance?
- What is lifetime risk?
- disease of adults and elderly
- single
- variable
- random mutations
- no (somatic)
- 1 in 3
basically what is going on here… i think… is that somewhere in our evolutionary past these chromosomes were linked up - but speication caused them to drift apart - so mutations that cause aren’t necessarily completely random - they are just reverting back to ancient forms in a sense … poissbily
