Cancer

Question 1

cancer critical genes

Answer 1

genes whose alteration results in cancer

2 broad types of mutations - over or under activity

Question 2

overactivity mutations

Answer 2

= gain of function

called oncogenes

Question 3

oncogenes

Answer 3

involve single mutational event and activation of gene causing proliferation

results in a gain of function

Question 4

underactivity mutations

Answer 4

= loss of function

called tumor suppressor genes

Question 5

tumor suppressor genes

Answer 5

involve genes that inhibit growth

mutation event - one = no effect, two = cancer

thus a recessive - must have both copies mutated for cancer

Question 6

benign vs. malignant tumor

Answer 6

both have uncontrolled growth but benign tumors are not invasive

Question 7

carcinomas

Answer 7

from epithelial cells

Question 8

sarcomas

Answer 8

from CT and muscle tissue

Question 9

leukemia and lymphomas

Answer 9

from WBCs and precursors

Question 10

metastases

Answer 10

when cancer cells break loose
enter a vessel
travel to new area

Question 11

DNA maintenance genes

Answer 11

• -subset of tumor suppressor genes
• -mutations = involve inactivation of caretaker genes
• -resulting in genome instability

Question 12

proto-oncogenes

Answer 12

normal genes required for cell division, growth, etc.

when hyperactivated = oncogene

Question 13

4 mechanisms for oncogene activation

Answer 13

1. deletion or point mutation
2. regulatory mutation
3. gene amplification
4. chromosomal rearrangement

Question 14

Ras oncogenes

Answer 14

cannot shut off by hydrolyzing GTP to GDP

Question 15

oncogene activation mutations

Answer 15

are dominant

only one allele needs to present for activity

Question 16

deletion/point mutation

Answer 16

in coding sequence

makes a hyperactive protein

ex. Ras codon 12 mutations turns Gly into Val = Ras is always in active form

Question 17

regulatory mutation

Answer 17

produce excess of normal protein

= promoter mutation

Question 18

gene amplification

Answer 18

make several copies instead of only 1

results in normal protein being overproduced

Question 19

chromosomal rearrangement

Answer 19

creates new regulatory sequence that causes overproduction or overactive fusion proteins

Question 20

example of chromosomal rearrangement mutation

Answer 20

EGF receptor
rearrangement removes it’s extracell domain

now active w/o needing ligand binding

fools cell into producing signals for division

associated w/ brain tumor - glioblastoma

Question 21

cellular functions of oncogenes

Answer 21

ligands
receptors
transcription factors
cell cycle proteins
proteins that inhibit apoptosis

Question 22

Bcl2 oncogene

Answer 22

example of rearrangement mutation

reciprocal translocation between chr 18 and 14

places Bcl2 gene under new control = greater expression

Question 23

Bcl2 oncogene result

Answer 23

B cell lymphoma
over active B cells
tumor development

Question 24

tumor suppressor genes generally encode proteins that ?

Answer 24

inhibit cell proliferation

Question 25

2 types of tumor suppressor genes

Answer 25

genes that restrict growth genes that maintain integrity of genome

Question 26

TSG - proteins that normally restrict cell growth and proliferation

Answer 26

- -they inhibit progression, checkpoints - -receptors or components in cell cycle that inhibit cycle - -or proteins that promote apoptosis, caspases

Question 27

TSG - proteins that maintain integrity of the genome

Answer 27

- -checkpoint control proteins, ATM, ATR - -AT gene - -DNA repair enzymes or pathways

Question 28

retinoblastoma cause

Answer 28

loss of both copies of Rb genes -- which are TSGs resulting in retina tumor Rb is a protein that inhibits cell division

Question 29

retinoblastoma forms

Answer 29

1. hereditary -- 40% | 2. sporadic -- 60%

Question 30

hereditary retinoblastoma

Answer 30

- -deletion of 1 Rb copy inherited - -event occurs to mutate 2nd copy - -tumor onset in both eyes

Question 31

sporadic retinoblastoma

Answer 31

- -not inherited - -all cells are normal - -2 hit hypothesis to mutate both copies - -tumor onset in one eye

Question 32

function of Rb

Answer 32

inhibits cell division by inactivating E2F via phosphorylation w/o Rb E2F is always active thus no control over division

Question 33

tumor suppressor mutations are ?

Answer 33

recessive | meaning both copies of gene must be mutated for cancer to develop

Question 34

prevention colon cancer

Answer 34

- -very preventable - -takes 10 years for tumor progression - -start colonoscopies at 50

Question 35

colorectal cancer characteristics

Answer 35

- -arises in epi lining lg intestine - -gut is renewed rapidly - -thus high chance for error

Question 36

colorectal cancer mutations

Answer 36

they disrupt organization signals and begin tumor progression

Question 37

polyp

Answer 37

a precursor to colorectal cancer cut off poly = cure if left cancer will develop

Question 38

common mutations of colorectal cancer

Answer 38

40% point mut. in K-Ras 60% inactivating mutation of p53 most important is Apc mutation resulting in loss of gene

Question 39

chemotherapy

Answer 39

stops cell division | affects rapidly growing cells most

Question 40

side effects of chemotherapy

Answer 40

good rapidly dividing cells also effected | ex. hair, stomach lining, blood producing cells

Question 41

Philadelphia chromosome

Answer 41

reciprocal translocation of chr 9 and 22 | = myologenous leukemia

Question 42

why does philadephia chromosome lead to CML?

Answer 42

it creates hybrid gene Bcr-Abl Abl is tyrosine kinase Bcr on N-terminus makes it hyperactive and is highly expressed resulting in cancer

Question 43

CML treatment

Answer 43

Gleevec inhibits tyrosine kinase activity it takes place of ATP on Bcr-Abl and blocks pathway thus no cell division signals produced no leukemia

Question 44

combination therapy

Answer 44

cancer may be resistant to some drugs thus treat w/ multiple drugs because cells are not resistant to all drugs