Block 3 Lecture 1 -- Cancer Overview

Question 1

What is transition mutation?

Answer 1

substitute purine for purine

Question 2

What are the purine nucleotides?

Answer 2

A, G (2 rings)

Question 3

What is a transversion mutation?

Answer 3

Substitute purine for pyrimidine or vice versa

Question 4

What are the single base mutations?

Answer 4

1) transition
2) transversion
3) insertion

Question 5

Define carcinogenesis:

Answer 5

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

Question 6

What are the steps in carcinogenesis?

Answer 6

1) initiation
2) promotion
3) progression

Question 7

What are cis-regulatory elements?

Answer 7

non-coding regions of DNA that regulate transcription

Question 8

What are trans-acting factors?

Answer 8

transcription factors that bind cis-regulatory elements

Question 9

Intron or exon…which is translated?

Answer 9

exon

Question 10

What is a mutagen?

Answer 10

substance that causes an alteration to DNA sequence

Question 11

What are the mutagenic products of UV light?

Answer 11

1) TT cyclobutane pyrimidine dimers

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

Question 12

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

Answer 12

CC to TT transition

Question 13

What forms of UV are most carcinogenic?

Answer 13

UVA and UVB

Question 14

Where are nitrosamines found?

Answer 14

pickled foods

Question 15

Where are polycyclic aromatic amines found?

Answer 15

large # found in tobacco smoke

Question 16

What pathogens can be carcinogenic?

Answer 16

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

Question 17

What are the types of mutations that may occur?

Answer 17

1) single base
2) deletion
3) translocations

Question 18

What is an enhancer?

Answer 18

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

Question 19

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

Answer 19

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

Question 20

What are the types of DNA repair?

Answer 20

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

Question 21

What is one-step DNA repair?

Answer 21

aka direct DNA repair

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

Question 22

When is nucleotide excision repair used?

Answer 22

when damage generates a bulky, helix-distorting mutation

– UV damage

Question 23

How are DNA/RNA tumor viruses carcinogenic?

Answer 23

encode proteins that block host cell tumor suppressor genes

Question 24

What molecules are known carcinogens?

Answer 24

1) polycyclic aromatic amines

2) nitrosamines

Question 25

How are polycyclic aromatic amines mutagenic?

Answer 25

- - generate cascade of metabolic epoxides | - - epoxides near the "bay region" between aromatic rings are genotoxic

Question 26

What type of cancer are nitrosamines linked to?

Answer 26

gastric

Question 27

How are nitrosamines carcinogenic?

Answer 27

alkylnitrosureas form oxygen adduct on guanine residues

Question 28

What is present in the 3' untranslated region?

Answer 28

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

Question 29

What is haploinsufficiency?

Answer 29

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

Question 30

What characteristics of electromagnetic radiation = higher energy?

Answer 30

higher frequency | shorter wavelength

Question 31

What endogenous reactions generate mutations?

Answer 31

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

Question 32

How does generation of an abasic site lead to mutations?

Answer 32

1) deamination of C to U | - - errors in replication, recombination

Question 33

What are the main six hallmarks of cancer?

Answer 33

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

Question 34

What are the other 4 hallmarks of cancer?

Answer 34

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

Question 35

What determines normal replicative potential?

Answer 35

defined number of doublings before sensescence | -- telomere length = Hayflick's limits

Question 36

How do cancer cells have unlimited replicative potential?

Answer 36

maintain telomere length

Question 37

How does inflammation promote tumors?

Answer 37

generate ROS

Question 38

How is energy metabolism re-programmed in cancer?

Answer 38

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

Question 39

How are growth inhibitory signals evaded in cancer?

Answer 39

acquired mutation or gene silencing

Question 40

What factors determine carcinogenesis in an individual?

Answer 40

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