Neoplasia 2 Molecular Basis of Cancer: Role of Genetic and Epigenetic Alterations

Question 1

what lies at the heart of carcinogenesis?

this can be caused by?

Tumor arises from? can it be passed on?

Answer 1

Question 2

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?

Answer 2

Question 3

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?

Answer 3

Question 4

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?

Answer 4

kind of a family tree of evolution

Question 5

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?

Answer 5

Question 6

all cancers display what hallmarks of cancer? (how many? type of change? list all)

Answer 6

Question 7

acquisition of genetic and epigenetic alterations that confer these hallmarks may be accelerated by? 2

Answer 7

Question 8

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?

Answer 8

Question 9

Question 10

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?

Answer 10

Question 11

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?

Answer 11

Question 12

Growth Factor receptors- what goes wrong here? leads to?

Answer 12

Question 13

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?

Answer 13

Question 14

treatment of ERBB2? EGFR/ALK?

why in advanced stages is a treatment not as good?

Answer 14

Question 15

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?

Answer 15

Question 16

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?

Answer 16

Question 17

BRAF and PI3K mutations

BRAF- member of what family? most common cancer? function? mutation causes?

PI3K- normal function? activates? is regulated by?

Answer 17

Question 18

Therapy strategy for RAS or BRAF?

Answer 18

Question 19

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?

Answer 19

Question 20

alterations in nonreceptor tyrosine kinases 2nd

point mutation example? function? treatment?

Answer 20

Question 21

Transcription factors

which ones are important for mutations?

why are transcription factors important for cancer?

Answer 21

Question 22

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?

Answer 22

Question 23

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?

Answer 23

Question 24

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?

Answer 24

Question 25

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?

Answer 25

Question 26

front and back

Answer 26

Question 27

RB- role normal? the ways RB function is compromised? second way explanation?

Answer 27

Question 28

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?

Answer 28

Question 29

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?

Answer 29

Question 30

P53 senses what? what usually keeps P53 in check? what removes the check? 2 1. what molecules? 2. pathway involved?

Answer 30

Question 31

Once activated p53 thwarts neoplastic transformation how? 3 key target gene functions? also what type of RNAS?

Answer 31

Question 32

outcomes of p53 accumulation? 3 1. cell cycle arrest- response to? caused by transcription of? this encodes for? this does what? 2. senescence- what is it? 3. apoptosis- occurs when? what genes encoded to do this? which pathway? how is the pathway chosen?

Answer 32

Question 33

With loss of P53 function what happens? irradiation and chemo vs p53? collaborators with p53?

Answer 33

Question 34

APC: gatekeeper of ______ works how? if faulty? part of what signalling pathway? major protein? function? if you lose APC?

Answer 34

Question 35

CDKN2A encode for? this does what? other thing encoded which does what? mutation affects what pathways? cancer association?

Answer 35

Question 36

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?

Answer 36

Question 37

WT1 loss of function associated with? chromosome? WT1 protein does what? what else shows WT1 ? interesting about this?

Answer 37

Question 38

pTCH aka? what is it? encodes for? involved in what pathway how? normal function? abnormal? cancer associated? treatment?

Answer 38

Question 39

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?

Answer 39