Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
52 Cards in this Set
- Front
- Back
|
what is a driver mutation?
|
a mutation that confers a growth or survival advantage
|
|
|
what 2 major classes of genes do driver mutations affect?
|
tumor suppressor genes
proto-oncogenes |
|
|
what are the 2 types of tumor suppressor genes mentioned?
|
gatekeeper genes
caretaker genes |
|
|
what are gatekeeper genes?
|
they interrupt the growth associated genes
or induce the death of the cell if damage is too great |
|
|
what are caretaker genes?
|
DNA repair proteins
|
|
|
how are tumor suppressor genes inactivated? (mutations)
|
loss of function mutations
|
|
|
what does loss of heterozygosity mean?
|
losing the last normal copy of a gene
|
|
|
what is unique about autosomal dominant cancer syndromes?
|
they are passed on in a recessive fassion, but 90% of the time create a second mutation that that completely inactivates the gene
|
|
|
what disease represents 3% of all pediatric cancers?
|
retinoblastoma
#1 eye cancer |
|
|
is retinoblastoma an autosomal dominant or recessive syndrome?
|
dominant
|
|
|
what gene is mutated in retinoblastoma?
|
Rb
|
|
|
how might one differentiate between familial and sporadic retinoblastoma without genetic tests?
|
family history and
Familial- bilateral sporadic- unilateral |
|
|
how is the single gene mutation, from an autosomal dominant synd, passed on to the second allele?
|
LOH mitotic recombination
mitotic recombination can pass the gene to the second chromosome |
|
|
what is the most important tumor suppressor in the body?
|
p53
|
|
|
what is p53?
|
a transcription factor
|
|
|
what does p53 do?
|
it promotes the synthesis of proteins that cause cell cycle arrest or apoptosis
|
|
|
how is p53 held at bay when there is no DNA damage?
|
mdm2 (ubiquitin ligase) binds free p53 and targets it for degradation
|
|
|
how is p53 activated?
|
ATM kinase phosphorylates p53 which stabilizes it and prevents mdm2 from binding
|
|
|
what does p53 do after being activated by ATM?
|
it binds to DNA and promotes the transcription of p21 and Bax
|
|
|
what causes the cell cycle to halt when there is DNA damage?
|
ATM activates p53
p53 upregulates p21 p21 inhibits cycE/cdk2 cell halted at restriction point |
|
|
where is the restriction point?
|
in the G1 phase
|
|
|
what do "death substrates" do?
|
they proteolyse cytoskeletal proteins
|
|
|
what are apoptotic caspases called?
|
executioner caspases
|
|
|
what is the first caspase to be activated during apoptosis?
|
caspase 9
|
|
|
what are the sequence of events that happen following irreparable Damage to cellular DNA?
|
ATM activates p53
p53 stimulates Bax and Apaf-1 cytochrome C is released from mitochondria and binds to Apaf-1 Apaf-1 assembles and joins procaspase-9 executioner caspases 3,6,7 are activated |
|
|
how does the cell keep itself from apoptosing if it only needs to repair DNA?
|
Bcl-2 (and other) proteins
|
|
|
what does Bcl-2 do?
|
closes the mitochondrial channels that release cytochrome C and prevents apoptosis
|
|
|
what are the majority of p53 mutations?
|
gain of function, missense mutations
p53 is still made, but function diminished |
|
|
what is affected in Li-Fraumeni syndrome?
|
p53
|
|
|
what are the chances that a person with Li-Fraumeni will develop cancer and what type of cancer will they develop?
|
90%
any and all cancers |
|
|
what tumor promoting proteins does HPV encode for?
|
E6
E7 |
|
|
what does E6 do?
|
HPV protein that destroys p53
cell proliferation |
|
|
what does E7 do?
|
HPV protein that causes the release of E2F by binding to Rb
cell proliferation |
|
|
what is gardasil?
|
a subunit vaccine that prevents cervical cancer by preventing HPV6,11,16,18 infections
|
|
|
What does a mutation in APC cause?
|
FAP (familial adenomatous polyposis
|
|
|
What happens in FAP?
|
hundreds to thousands of polyps form in the colon
|
|
|
What must be done to an individual with FAP?
|
the colon must be removed or they will develop colorectal cancer
|
|
|
What is the role of APC in the cell?
|
binds to and destroys B-catenin , preventing it from promoting growth gene transcription
|
|
|
what happens to APC when a WNT signal is recieved?
|
The APC complex doesnt form and B-catenin promotes growth gene transcription
|
|
|
where does the colon maintain a WNT rich environment?
|
in the crypts of colon endothelial cells
|
|
|
where does the body usually maintain a WNT free environment
|
the lumenal surface of colon endothelium, away from the crypts
|
|
|
which cells secret the WNT signal?
|
stromal cells in the colon crypts
|
|
|
what does the NF1 family of genes make?
|
GAP proteins
|
|
|
what does GAP do?
|
deactivates Ras by stimulating Ras GTPase activity
|
|
|
what do BRCA1 and 2 do?
|
they are DNA repair proteins that work via homologous recombination
|
|
|
what type of cancers do mutations of BRCA1 and 2 proteins lead to?
|
breast and ovarian
|
|
|
what is HNPCC
|
heriditary non-polyposis colon cancer
|
|
|
what is the difference in FAP and HNPCC?
|
FAP causes colon cancer caused by mutations in APC
HNPC causes colon cancer by mutations in Mlh-1 and MSH-2. carcinomas occur much faster in this case though |
|
|
what do Msh-2 and Mlh-1 do?
|
strand directed mismatch repair
|
|
|
is xeroderma pigmentosa an autosomal dominant or recessive synd?
|
recessive (like the only one)
|
|
|
what happens in Xeroderma pigmentosa
|
pyrimidine dimers form and are not repaired by the nucleotide excision pathway
|
|
|
how much higher is an XP patients risk of skin cancer? tongue cancer?
|
skin-1000X
tongue 100,000X |
