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22 fall: path > Test 1: lecture 10 genetics of cancer > Flashcards

Test 1: lecture 10 genetics of cancer Flashcards

1
Q

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

A

oncogenes
foot on the accelerator.

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2
Q

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

A

tumor suppressor genes
brake is broken.

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3
Q

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

A

telomerase
telomere

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4
Q

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

A

anti-apoptotic genes

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5
Q

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

A

Vascular Endothelial Growth Factors (VEGF)

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6
Q

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

A

basement membrane

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7
Q

6 ways cancers have evolved to survive

A

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

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8
Q

what are some extrinsic environmental exposures that cause cancer

A

gamma

UV light

second hand smoke

chemicals (asbestos)

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9
Q

what are some extrinsic factors that cause cancer

A

environmental : gamma, UV, smoke, chemicals

Infectious: viruses, ect

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10
Q

what are the 3 etiologies of feline squamous cell carcinoma

A

80% UV light exposure

53% p53 mutations (mutate tumor suppressor gene)

80% infection with papillomavirus

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11
Q
A
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12
Q

how do retroviruses cause cancer

A

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

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13
Q

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

A

insertional mutagenesis

viral promoter

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

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14
Q

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

A

MYC

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15
Q

how is rous sarcome virus different from other retroviruses

A

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

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16
Q

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

A

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

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17
Q

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

A

rou’s sarcoma virus

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

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18
Q

what 4 type of genes are involved in cancer

A

proto-oncogenes → drive cancer

tumor- suppressor genes

apoptosis gene

DNA repair genes

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19
Q

what are some common oncogenes

A

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

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20
Q

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

A

oncogenes

uncontrolled cell growth

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21
Q

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

A

dominant

one copy

22
Q

MYC is a ___

A

proto-oncogene that is a master transcription factor

regulates genes that control cellular proliferation

when it is mutated causes uncontrolled cell growth

23
Q

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

A

EGFR, RAS, cKIT

Myc, NF-kB

CDK, cyclin

24
Q

EGFR is a ___

A

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

25
Q

CDK is a __

A

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

26
Q

what receptor mutates in mast cell tumor?

A

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

27
Q

c-KIT mutations in common in what cancer type

A

mast cell tumor

tyrosine kinase receptor that mutates to cause uncontrolled cell growth

28
Q
A

Mast cell tumor

c-KIT → tyrosine kinase receptor

29
Q

what drug targets cKIT and what cancer is it targeting?

A

palladia (toceranib)

mast cell tumors

tyrosine kinase inhibitor

30
Q

palladia(toceranib) targets ____

A

tyrosine kinase inhibitor

cKIT, VEGFR, PDGFR

tumor types: mast cell, sarcomas, carcinomas, melanomas, myeloma

31
Q

gleevec (imatinib) and Kinavet (masitinib) target

A

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

32
Q

what happens in Burkitts lympoma

A

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

33
Q

what happens in DLBCL

A

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

34
Q

chronic myelogenous leukemia (CML)

A

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

35
Q

imatinib

A

drug to inhibit BCR-ABL found in CML

prevents tyrosine kinase from phosphorylation

(chronic myelogenous leukemia aka philadelphia chromosome 9:22)

36
Q

How does NF-KB work

A

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

37
Q

what are some common tumor suppressor genes

A

p53, NF1, BRCA, retinoblastoma

38
Q

for a tumor suppressor gene to cause cancer it needs ___

A

both alleles need to be mutated → recessive

39
Q

how does p53 work

A

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

40
Q

Rb

A

retinoblastoma

tumor suppressor gene

prevents excessive cell growth by holding E2F which halts cell cycle

41
Q

NF-1

A

tumor suppressor gene

inactivates RAS

42
Q

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

A

p53 → tumor suppression gene

p21 →stops cell cycle

GADD45→ repair DNA

Bax→ apoptosis

43
Q

how does Rb work

A

tumor suppression gene

Rb produces Rb that hold E2F in place and prevents cell cycle

E2F controls the transition from G1 to S phase

44
Q

how do viruses inactivate p53 and Rb

A

produce E7 that binds to Rb

E6 binds to p53

inactivates the tumor suppressing genes

45
Q

Bcl-2

A

anti-apoptotic gene

blocks the release of cytochrome C from the mitochondria

46
Q

follicular lymphoma is caused by the translocation of ___

A

Bcl-2 from chromosome 14 to 18

leads to an increase in the anti-apoptotic gene → cell does not die

(non-hodgkin lymphoma)

47
Q

greyhounds get ___

goldens get ___

bernese mountain dogs get ___

A

osteosarcoma

lymphosarcoma

histiocytic sarcoma

48
Q

VEGF

A

causes angiogenesis → new vessel growth

49
Q

thrombospondin and angiostatin cause ___

A

inhibit angiogenesis

50
Q

what drug is used for mast cell tumors

A

palladia (toceranib) block ckit tyrosine kinase receptor

51
Q

what medicine is used for HSA

A

copanlisib (aliqopa)

PIK3CA mutations

52
Q

what treatment for urothelial carcinoma

A

zelboraf (vemurafenib)

BRAF mutation (RAS pathway)

22 fall: path (46 decks)

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