Block 3 Lecture 1 -- Cancer Overview Flashcards

1
Q

What is transition mutation?

A

substitute purine for purine

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2
Q

What are the purine nucleotides?

A

A, G (2 rings)

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3
Q

What is a transversion mutation?

A

Substitute purine for pyrimidine or vice versa

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4
Q

What are the single base mutations?

A

1) transition
2) transversion
3) insertion

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5
Q

Define carcinogenesis:

A

the steps by which a normal cell is transformed into a cancer cell

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6
Q

What are the steps in carcinogenesis?

A

1) initiation
2) promotion
3) progression

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7
Q

What are cis-regulatory elements?

A

non-coding regions of DNA that regulate transcription

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8
Q

What are trans-acting factors?

A

transcription factors that bind cis-regulatory elements

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9
Q

Intron or exon…which is translated?

A

exon

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10
Q

What is a mutagen?

A

substance that causes an alteration to DNA sequence

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11
Q

What are the mutagenic products of UV light?

A

1) TT cyclobutane pyrimidine dimers

2) TC (6-4) pyrimidine-pyrimidone photoproducts

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12
Q

What is the signature mutation of TC (6-4) pyrmidine-pyrimidone products?

A

CC to TT transition

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13
Q

What forms of UV are most carcinogenic?

A

UVA and UVB

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14
Q

Where are nitrosamines found?

A

pickled foods

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15
Q

Where are polycyclic aromatic amines found?

A

large # found in tobacco smoke

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16
Q

What pathogens can be carcinogenic?

A

1) Kaposi’s sarcoma-associated herpesvirus
2) HBV
3) H. pylori

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17
Q

What are the types of mutations that may occur?

A

1) single base
2) deletion
3) translocations

18
Q

What is an enhancer?

A

a cis-regulatory element that recruits proteins to initiate specific gene transcription

19
Q

What is present in the 5’ un-translated region (UTR)?

A

1) high GC content – hairpin loops
2) cis-reg elements
3) Kozak initiation sequence

20
Q

What are the types of DNA repair?

A

1) NER
2) BER
3) mismatch
4) recombinational
5) one-step repair

21
Q

What is one-step DNA repair?

A

aka direct DNA repair

    • reversal of base methylation
    • O6-alkylguanine-DNA-alkyltransferase sacrifices self to transfer methyl/ethyl to own Cys residue
22
Q

When is nucleotide excision repair used?

A

when damage generates a bulky, helix-distorting mutation

– UV damage

23
Q

How are DNA/RNA tumor viruses carcinogenic?

A

encode proteins that block host cell tumor suppressor genes

24
Q

What molecules are known carcinogens?

A

1) polycyclic aromatic amines

2) nitrosamines

25
Q

How are polycyclic aromatic amines mutagenic?

A
    • generate cascade of metabolic epoxides

- - epoxides near the “bay region” between aromatic rings are genotoxic

26
Q

What type of cancer are nitrosamines linked to?

A

gastric

27
Q

How are nitrosamines carcinogenic?

A

alkylnitrosureas form oxygen adduct on guanine residues

28
Q

What is present in the 3’ untranslated region?

A

AAUAAA signal
– directs addition of Poly-A tail for stability
miRNA binding sites

29
Q

What is haploinsufficiency?

A

single gene doesn’t express enough protein for wild-type phenotype
– can be result of 1 allele mutation of a tumor suppressor gene

30
Q

What characteristics of electromagnetic radiation = higher energy?

A

higher frequency

shorter wavelength

31
Q

What endogenous reactions generate mutations?

A

1) oxidative respiration (ROS)
2) lipid peroxidation (ROS)
3) spontaneous glycosidic bond hydrolysis (abasic site)

32
Q

How does generation of an abasic site lead to mutations?

A

1) deamination of C to U

- - errors in replication, recombination

33
Q

What are the main six hallmarks of cancer?

A

1) growth signal autonomy
2) evasion of growth inhibitory signals
3) evasion of apoptosis
4) angiogenesis
5) unlimited replicative potential
6) invasion and metastasis

34
Q

What are the other 4 hallmarks of cancer?

A

1) genome instability and mutation
2) reprogramming energy metabolism
3) tumor-promoting inflammation
4) avoiding immune destruction

35
Q

What determines normal replicative potential?

A

defined number of doublings before sensescence

– telomere length = Hayflick’s limits

36
Q

How do cancer cells have unlimited replicative potential?

A

maintain telomere length

37
Q

How does inflammation promote tumors?

A

generate ROS

38
Q

How is energy metabolism re-programmed in cancer?

A

glycolysis even in presence of O2 due to high fuel and precursor demand

39
Q

How are growth inhibitory signals evaded in cancer?

A

acquired mutation or gene silencing

40
Q

What factors determine carcinogenesis in an individual?

A

1) net cell number
- - cell proliferation, differentiation, death
2) environmenet
3) reproductive life
4) diet
5) smoking