Neoplasia 2 Molecular Basis of Cancer: Role of Genetic and Epigenetic Alterations Flashcards
what lies at the heart of carcinogenesis?
this can be caused by?
Tumor arises from? can it be passed on?
4 classes of normal regulatory genes?
what are each involved in?
cause cancer via? (how does each of the 4 turn into cancer)
what is a mutator phenotype? this is marked by?
carcinogenesis results from?
malignant neoplasms phenotype referred to as cancer hallmarks? 3
mutations that contribute to develop of malignant phenotype is called? whats an initiating mutation?
just one mutation to be cancer?
cancer arise from what type of cells?
common early step on road to malignancy? (especially solid tumors) how?
whats a passenger mutation?
tumors evolve? under what selection?
how is this so? who wins? this is referred to as?
After DNA sequencing of primary tumors what two types of mutations were identified?
creates?
speed of evolution?
kind of a family tree of evolution
selection of fittest cells explains what?
other than DNA mutations what also contribute to malignant properties of cancer cells? what is this? 2
these 2 dictate what?
which is responsible for silencing some tumor suppressor genes?
are these type reversible?
all cancers display what hallmarks of cancer? (how many? type of change? list all)
acquisition of genetic and epigenetic alterations that confer these hallmarks may be accelerated by? 2
self sufficiency in growth signals: oncogenes
what is an oncogene? proto-oncogene?
oncogenes encode for? these have what function? what factor allows them to proliferate excessively?
(some growth factor pathway review if you want)
aberrations in signalling pathways? makes? kept in check usually by?
we focus on which receptor?
Proto-oncogenes, Oncogenes, and Oncoproteins
darwinian selection picks factors with greatest impact on malignant phenotype
so for tyrosine kinase pathway what are the big players?
Proto-oncogenes, Oncogenes, and Oncoproteins
growth factors- normal stim by them? some cancers though? type of signalling?
ex?
in these forms what causes secretion of these growth factors?
Growth Factor receptors- what goes wrong here? leads to?
important growth factor receptor mutations: 3
what do each encode for? major cancer involved?
3rd one a little different- what is it? causes? type of cancer?
treatment of ERBB2? EGFR/ALK?
why in advanced stages is a treatment not as good?
downstream components of receptor tyrosine kinase signaling pathway. 2 main?
type of mutation?
when RAS is gain of function what happens for normal signalling pathway?
specific cancer?
Most common type of abnormality involving proto-oncogenes in human tumors? the three gnees in humans?
most common cancer?
normal function of RAS?
with a mutation? same outcome if what other mutation? ex?
BRAF and PI3K mutations
BRAF- member of what family? most common cancer? function? mutation causes?
PI3K- normal function? activates? is regulated by?
Therapy strategy for RAS or BRAF?
alterations nonreceptor Tyrosine kinase
mutations often take the form of?
important example of this? 2 what genes? chromosomes? this creates? BCR important for?
treatment of CML? why so effective?
does this lead to cure? why? so must do what?
alterations in nonreceptor tyrosine kinases 2nd
point mutation example? function? treatment?
Transcription factors
which ones are important for mutations?
why are transcription factors important for cancer?
MYC oncogene- expressed in what cells? induced by? mutation where for what cancers?
MYC activates expression of what? master transcriptional regulator of?
MYC upregs what? other oncogenic role?
cancers that can have MYC problems?
other than a direct mutation in MYC how else can we have increased MYC?
cyclin and cyclin-dependent kinases
function? antagonist?
two main cell cycle checkpoints? one closely associated with cancer?
two mutations that cause that checkpoint to be faulty? examples
two most important tumor suppressors?
products of tumor suppressor genes do what?
2 examples of tumor suppressors? recognize what stress? what do they do to such cells?
RB found studying what cancer?
what is knudson’s two hit hypothesis of oncogenesis?
(for RB)
familial cases?
sporadic cases?
inherited RB do you have cancer with one? what increases? whats normal?
front and back
RB- role normal? the ways RB function is compromised?
second way explanation?
RB associated with what cancers?
why arent RB mutations found in all kinds of cancer?
what is key to malignant transformation? thus one of four (what are they) is usually lost?
what type of disease process also fuck up RB?
of note? specific protein?
most frequently mutated gene in human cancers? regulates what? specific area of mutation?
inherited? most common tumors? (name for inherited)
encodes what protein? Mutation that affects this proteins regulation?
viral protein that degrades it?
P53 senses what? what usually keeps P53 in check?
what removes the check? 2
- what molecules?
- pathway involved?
Once activated p53 thwarts neoplastic transformation how?
3 key target gene functions?
also what type of RNAS?
outcomes of p53 accumulation? 3
- cell cycle arrest- response to? caused by transcription of? this encodes for? this does what?
- senescence- what is it?
- apoptosis- occurs when? what genes encoded to do this? which pathway?
how is the pathway chosen?
With loss of P53 function what happens?
irradiation and chemo vs p53?
collaborators with p53?
APC: gatekeeper of ______ works how?
if faulty?
part of what signalling pathway?
major protein? function?
if you lose APC?
CDKN2A
encode for? this does what? other thing encoded which does what?
mutation affects what pathways?
cancer association?
NF1 vs NF2
1- if mutant develop what? called? protein product normally? does what? so without it?
2- development of? where? what proteins? do what? so if lacking?
WT1
loss of function associated with? chromosome?
WT1 protein does what? what else shows WT1 ?
interesting about this?
pTCH aka?
what is it? encodes for? involved in what pathway how? normal function? abnormal?
cancer associated?
treatment?
VHL
germline loss of function leads to? chromosome?
VHL protein function? key protein?
in what environment will it be overexpressed?
this causes what genes to be activated?
cancer?
