Test 1: lecture 10 genetics of cancer

Question 1

Self-sufficiency of growth signals
Activating mutations in ____(autonomous growth)
Car Analogy: ____

Answer 1

oncogenes
foot on the accelerator.

Question 2

Insensitivity to anti-growth signals
Deactivating mutations in ____
Car analogy: ___

Answer 2

tumor suppressor genes
brake is broken.

Question 3

Limitless replicative potential –
Abnormal/decreased expression of ____ - prevents ___shortening that normally would induce cellular senescence /death.

Answer 3

telomerase
telomere

Question 4

Evasion of Apoptosis
Mutations in apoptotic genes or over-expression of ____ allow cancer cells to escape apoptosis

Answer 4

anti-apoptotic genes

Question 5

Angiogenesis
New blood vessel growth to the site of the tumor, allowing
the cells to get oxygen and nutrients
___

Answer 5

Vascular Endothelial Growth Factors (VEGF)

Question 6

Tissue Invasion and Metastasis
Tumor cells break the ___ and invade the
ECM, spread to distant sites via the blood stream or lymphatics

Answer 6

basement membrane

Question 7

6 ways cancers have evolved to survive

Answer 7

mutate growth signals → oncogenes

stop anti-growth signals → turn off tumor suppressor genes

prevent telomere shortening → lives forever

prevents cell death → mutate apoptotic genes and increased production of anti-apoptotic genes

increase blood vessels to area → feed itself (VEGF)

Metastasis

Question 8

what are some extrinsic environmental exposures that cause cancer

Answer 8

gamma

UV light

second hand smoke

chemicals (asbestos)

Question 9

what are some extrinsic factors that cause cancer

Answer 9

environmental : gamma, UV, smoke, chemicals

Infectious: viruses, ect

Question 10

what are the 3 etiologies of feline squamous cell carcinoma

Answer 10

80% UV light exposure

53% p53 mutations (mutate tumor suppressor gene)

80% infection with papillomavirus

Question 11

Answer 11

Question 12

how do retroviruses cause cancer

Answer 12

retrovirus invades cell

reverse transcribes its viral RNA into pro-viral DNA

invades the nucleus and inserts itself onto the hosts DNA

over takes the host machinery to make proteins for itself

in cancers will insert promotors upstream from genes that will increase cell growth → uncontrolled growth of the cell

activate oncogenes by inserting next to them and driving their expression from powerful viral promoters

Question 13

retrovirues cause cancer by activating oncogenes through ___. Which means they activate oncogenes by inserting next to them and driving their expression by the ___

Answer 13

insertional mutagenesis

viral promoter

feline T cell lymphoma is caused by viral promotor that mutates MYC to cause uncontrolled proliferation

Question 14

feline T cell lymphoma is caused by viral promotor that mutates___ to cause uncontrolled proliferation

Answer 14

MYC

Question 15

how is rous sarcome virus different from other retroviruses

Answer 15

backwards

normally virus will bind to host DNA and take over

in rous- piece of host DNA SRC gene (tyrosine kinase/oncogene) attaches to viruses RNA and leads to uncontrolled growth

Question 16

what gene is transferred to viral genome in rous sarcoma virus?

Answer 16

SRC gene (tyrosine kinase/ oncogene) → leads to uncontrolled growth

Question 17

___ Rare recombination event in which part of the viral genome is replaced by a cellular proto-oncogene

Answer 17

rou’s sarcoma virus

transfer of host SRC gene (tyrosine kinase/oncogene) to the virus

Question 18

what 4 type of genes are involved in cancer

Answer 18

proto-oncogenes → drive cancer

tumor- suppressor genes

apoptosis gene

DNA repair genes

Question 19

what are some common oncogenes

Answer 19

Growth factor receptor: Ras, EGFR

Transcription factor: Myc, NFKB

Cell cycle regulator: CDK

these are proto-oncogenes that have been mutated to cause unregulated cell growth

only need one mutated copy to get uncontrolled cell growth

c-Kit → mast cell tumor

MYC→ lymphoma

NFKB→ DLBCL

Question 20

proto-oncogenes that have been mutated are called ___. they cause ___

Answer 20

oncogenes

uncontrolled cell growth

Question 21

oncogenes are ___ and need how many copies of the mutation to cause uncontrolled cell growth?

Answer 21

dominant

one copy

Question 22

MYC is a ___

Answer 22

proto-oncogene that is a master transcription factor

regulates genes that control cellular proliferation

when it is mutated causes uncontrolled cell growth

Question 23

proto- oncogenes can be growth factor receptors (___), transcription factors (____) and cell cycle regulators (____)

Answer 23

EGFR, RAS, cKIT

Myc, NF-kB

CDK, cyclin

Question 24

EGFR is a ___

Answer 24

growth factor receptor (tyrosine kinase receptor) that sits on the outside of the cell and when triggered will activate intracellular cascade through the G protein and Ras pathway to increase cell growth

when mutated (oncogene) leads to uncontrolled cell growth

Question 25

CDK is a \_\_

Answer 25

proto-oncogene that controls **cell cycle progression** from G phase to S phase oncogene will cause mutation that will cause cell to continuously grow and not stop to allow time for DNA repair

Question 26

what receptor mutates in mast cell tumor?

Answer 26

cKIT→ tyrosine kinase receptor that usually binds to SCF and dimerizes to trigger proliferation signal in the cell it can mutate to dimerize without its ligand or can mutate to just send the proliferation signal

Question 27

c-KIT mutations in common in what cancer type

Answer 27

mast cell tumor **tyrosine kinase receptor** that mutates to cause uncontrolled cell growth

Question 28

Answer 28

Mast cell tumor **c-KIT** → tyrosine kinase receptor

Question 29

what drug targets cKIT and what cancer is it targeting?

Answer 29

palladia (toceranib) mast cell tumors **tyrosine kinase inhibitor**

Question 30

palladia(toceranib) targets \_\_\_\_

Answer 30

**tyrosine kinase inhibitor** **cKIT**, VEGFR, PDGFR tumor types: **mast cell**, sarcomas, carcinomas, melanomas, myeloma

Question 31

gleevec (imatinib) and Kinavet (masitinib) target

Answer 31

tyrosine kinase inhibitor → cKIT Mast cell tumors **gleevec** → human med **kinavet** → not on the market **palladia/ toceranib**→ current med used for canine Mast cell tumors

Question 32

what happens in Burkitts lympoma

Answer 32

**chromosomal transmutation** of the **MYC oncogene** from chromosome 8 to chromosome 14 **Ig promotor** on chromosome 14 will cause Myc to overwork → uncontrolled cell growth **starry sky** appearance on histopath of pale macrophages and dark purple lymphocytes (B cells) similar to DLBCL in dogs

Question 33

what happens in DLBCL

Answer 33

diffuse large B cell lymphoma **chromosomal transmutation** of the **MYC oncogene** from chromosome 8 to chromosome 14 **Ig promotor** on chromosome 14 will cause Myc to overwork → uncontrolled cell growth **starry sky** appearance on histopath of pale macrophages and dark purple lymphocytes (B cells) **similar to Burkitt's lymphoma in humans**

Question 34

chronic myelogenous leukemia (CML)

Answer 34

philadelphia chromosome (9:22) parts of chromosome 9 (Abl) and 22 (Brc) fuse together creating Bcr-ABL tyrosine kinase cause over production of Abl gene → leads to uncontrolled cell growth **imatinib** is a drug that will inhibit BCr-ABL tyrosine kinase from phosphorylating

Question 35

imatinib

Answer 35

drug to inhibit BCR-ABL found in CML prevents tyrosine kinase from phosphorylation (chronic myelogenous leukemia aka philadelphia chromosome 9:22)

Question 36

How does NF-KB work

Answer 36

**master transcription factors** that regulate hundreds of genes involved in cellular proliferation inactive in the cytoplasm- phosphorylated then into nucleus and cause cell growth, anti-apoptotic genes, cytokines, and chemokines

Question 37

what are some common tumor suppressor genes

Answer 37

p53, NF1, BRCA, retinoblastoma

Question 38

for a tumor suppressor gene to cause cancer it needs \_\_\_

Answer 38

both alleles need to be mutated → recessive

Question 39

how does p53 work

Answer 39

stops and tries to fix/repair cell if it can't will trigger apoptosis tumor-suppressor gene → transcription factor that regulates expression of genes that block cell cycle or induce apoptotic cell death

Question 40

Rb

Answer 40

retinoblastoma tumor suppressor gene prevents excessive cell growth by holding E2F which halts cell cycle

Question 41

NF-1

Answer 41

tumor suppressor gene inactivates RAS

Question 42

Mutations in ___ frequently result in its inability to bind to target genes p21, Bax and GADD45

Answer 42

p53 → tumor suppression gene p21 →stops cell cycle GADD45→ repair DNA Bax→ apoptosis

Question 43

how does Rb work

Answer 43

tumor suppression gene Rb produces Rb that hold E2F in place and prevents cell cycle E2F controls the transition from G1 to S phase

Question 44

how do viruses inactivate p53 and Rb

Answer 44

produce **E7** that binds to Rb **E6** binds to p53 **inactivates the tumor suppressing genes**

Question 45

Bcl-2

Answer 45

anti-apoptotic gene blocks the release of cytochrome C from the mitochondria

Question 46

follicular lymphoma is caused by the translocation of \_\_\_

Answer 46

Bcl-2 from chromosome 14 to 18 leads to **an increase** in the anti-apoptotic gene → cell does not die (non-hodgkin lymphoma)

Question 47

greyhounds get \_\_\_ goldens get \_\_\_ bernese mountain dogs get \_\_\_

Answer 47

osteosarcoma lymphosarcoma histiocytic sarcoma

Question 48

VEGF

Answer 48

causes angiogenesis → new vessel growth

Question 49

thrombospondin and angiostatin cause \_\_\_

Answer 49

inhibit angiogenesis

Question 50

what drug is used for mast cell tumors

Answer 50

palladia (toceranib) block ckit tyrosine kinase receptor

Question 51

what medicine is used for HSA

Answer 51

copanlisib (aliqopa) PIK3CA mutations

Question 52

what treatment for urothelial carcinoma

Answer 52

zelboraf (vemurafenib) BRAF mutation (RAS pathway)