Oncogenes and Tumor Suppressors

Question 1

oncogenes

Answer 1

gain of function mutation in protooncogene.

Question 2

how many copies of oncogene needed?

Answer 2

Dominant on molecular level

Question 3

oncogenes are rarely inherited because

Answer 3

distort fetal growth: not compatible with life.

Question 4

types of genes effected (to become onco)

Answer 4

signal transduction pathways, growth factor receptors

Question 5

RAS

Answer 5

mutant in 30% of cancers. GTPase in signal trans. Pathway can become hyperactive to continually signal growth

Question 6

tumor suppressor genes

Answer 6

loss of function mutations

Question 7

how many mutated copies of suppressor needed?

Answer 7

two in same cell: recessive molecularly

Question 8

one mutated copy

Answer 8

increased risk for cancer

Question 9

genes effected by suppressor mutations

Answer 9

growth restriction genes, cell cycle check points, DNA repair genes

Question 10

p53

Answer 10

cell cycle checkpoints and apoptosis

Question 11

p53 expressed when

Answer 11

DNA is damaged. Pauses mitosis. Allows mismatch repair

Question 12

p53 allows repair how?

Answer 12

activates p21, which blocks phosphorylatoin of RB by cyclinD/CDK4.

Question 13

DNA repair occurs by

Answer 13

MSH2 complex called MMR mismatch repair

Question 14

p53 also activates cell death via

Answer 14

Bax

Question 15

BAD

Answer 15

pro-apoptotic death cell

Question 16

If BAD is knocked out

Answer 16

B-cell tumors!

Question 17

BAD & Epstein-Bar virus

Answer 17

Epstein-Bar virus drives B-cell production, causes leukemia in pt. without BAD

Question 18

Rb1

Answer 18

cell cycle checkpoint: inherited retinoblastoma

Question 19

BRCA1/2

Answer 19

DNA repair: inherited breast cancers. Does not explain sporadic cancers

Question 20

dysplacia

Answer 20

ADENOMA. Architecture preserved, subcellular organization is changing

Question 21

hyperplasia

Answer 21

CARCINOMA. More pronounced loss of architecture and organization

Question 22

colon cancer mutation sequence

Answer 22

1. loss of APC 2. hyperactive kRAS 3. DCC 4. p53

Question 23

Familial Adenomatosis Polyposis

Answer 23

inherited APC mutation

Question 24

APC mutation

Answer 24

many small growths

Question 25

HNPCC mutation (DNA repair)

Answer 25

adenomas rapidly convert to signle carinomic masses

Question 26

Avastin

Answer 26

anti-VEGF (tumor microenvironment inhibitor)

Question 27

Sunitinib

Answer 27

binds all VEGFRs and PDGFR KT

Question 28

DLL4 blockade

Answer 28

blocks stalk cell formation: useless vessels

Question 29

Herceptin

Answer 29

(general oncoprotein inhibitor) Ab, stops Her2/neu receptor dimerization

Question 30

Gleevac

Answer 30

(aka STI571: personalized) targets oncogenic kinase in Philadephia chromosome disease (chronic myelogenous leukemia)

Question 31

Gleevac fits

Answer 31

BCR-ABL oncogene, and c-Kit receptor for stem cell factor (a growth factor)

Question 32

Gleevac binds

Answer 32

ATP binding site within kinases

Question 33

Luminal A&B breast cancer

Answer 33

start in the lumen of mammary ducts

Question 34

Basal-like breast cancer

Answer 34

cells similar to outer layer of mammary ducts

Question 35

Her2E breast cancer

Answer 35

genetic, poor prognosis, early development