Cancer Stem Cells and Epigenetics (5,10,11) Flashcards Preview

CEDB30004 Stem Cells in Development and Regeneration > Cancer Stem Cells and Epigenetics (5,10,11) > Flashcards

Flashcards in Cancer Stem Cells and Epigenetics (5,10,11) Deck (45):
1

What is not a characteristic of a malignant tumour?
a. All cells demonstrate the same, reproducible mutation
b. There are different cell populations
c. Cells can be a different state of differentiation
d. Variability is genetic and non-genetic in nature




a. All cells demonstrate the same, reproducible mutation

2

What best describes a theory for how tumours can develop heterogeneity?
a. The cancer stem cell theory is based on the idea that CSCs and non-CSCs can convert to one another continuously
b. The clonal evolution theory suggests that because heritable genetic and epigenetic changes are favoured in response to microenvironment pressures
c. The plastic stem cell theory suggests that Cancer cells in tumour reside in different states of stemness and differentiation
d. The cancer stem cell theory has been proved without argument

b. The clonal evolution theory suggests that because heritable genetic and epigenetic changes are favoured in response to microenvironment pressures

3

What is not a feature of cancer stem cells?
a. They are tumour cells with stem cell properties
b. They are resistant to chemotherapy
c. They can drive tumour growth and metastases
d. They are easily studied due to their well-known origin and marker profile

d. They are easily studied due to their well-known origin and marker profile

4

What would not be found in a tumour niche?
a. Vascular network
b. Secreted factors
c. Limited stromal cells
d. Extracellular matrix

c. Limited stromal cells

5

How do exosomes and microvesicles compare?
a. They are the same size and density, but only exosomes use exocytosis
b. Microvesicles are much larger (100-1000nm) than exosomes (30-100nm)
c. Exosomes use blebbing whilst microvesicles use exocytosis
d. Exosomes are more dense than microvesicles

b. Microvesicles are much larger (100-1000nm) than exosomes (30-100nm)

6

What is true about diagnosing Pancreatic Cancer using extracellular vesicles?
a. It is not yet possible to distinguish benign from precancerous
b. The test is based on the EV membrane bound proteoglycan, GPC1
c. Glypican-1 is absent in the sera of patients with pancreatic cancer
d. Invasive sampling of the pancreatic tissue is needed to look for GPC1

b. The test is based on the EV membrane bound proteoglycan, GPC1

7

• Tumours are heterogeneous because they have different cell populations with different mutations, different states of differentiation, different functions and genetic and non-genetic variability.

T

8

• Cancer stem cells do not counteract the effectof drugs that specifically kill tumour cells.

F

9

• Cancer stem cells express Oct4, Sox2 and NANOG.

T

10

What is false about X inactivation and epigenetics?
a. A XXX female will have 3 barr bodies.
b. Changes are due to gene expression and not DNA sequence
c. Changes can be preserved through multiple cell divisions
d. A random X chromosome is inactivated in each cell of the embryo


a. A XXX female will have 3 barr bodies. (2)

11

What can methylation NOT lead to?
a. The recruitment of factors that modify histones
b. Nucleosomes forming tight complexes with DNA to block transcription factor binding
c. Gene activation at AT rich regions
d. The ability to differentiate a newly synthesised DNA strand from it’s template

c. Gene activation at AT rich regions

12

How do RNA polymerase and transcription factors access DNA?
a. When they are highly condensed as 30nm fibres
b. Following methylation of histone tails which decondenses nucleosomes
c. When the histone tails are cleaved by a transcription protease
d. Following acetylation which uncondenses nucleosomes

d. Following acetylation which uncondenses nucleosomes

13

What happens following the modification of histone tails?
a. The state of chromatin compaction is affected
b. Binding sites for chromatin modifying proteins are blocked
c. Polycomb protein is expressed ubiquitously
d. The methylation site is always phosphorylated

a. The state of chromatin compaction is affected

14

What is false about Polycomb protein?
a. It binds H3Me3K27
b. It is part of a polycomb repressor complex
c. It acts to enhance transcription
d. It maintains the repression of hox gene expression in specific developing body segments

c. It acts to enhance transcription

15

What is involved in the developmental consequences of DNA methylation?
a. In X chromosome inactivation, the inactive chromosome is not inherited
b. Genomic imprinting follows mendelian rules
c. Imprinting is due to differential methylation
d. Female germ cells are remethylated during meiosis in the embryonic gonad

c. Imprinting is due to differential methylation

16

How does insulin-like growth factor 2 demonstrate imprinting?
a. WT sperm and mutant Igf2 eggs produce small offspring
b. Mutant Igf2 sperm and WT eggs produce normal offspring
c. It is expressed from the female chromosome
d. Small offspring are produced from Igf2 mutant sperm and WT eggs

d. Small offspring are produced from Igf2 mutant sperm and WT eggs

17

What plays a role in considering if IPS cells have similar epigenomes to ES cells?
a. iPS cells must erase all methylation marks to revert to pluripotency
b. ES and iPS cells have exacly the same methylation patterns
c. The reversion process leads to non-random methylation events
d. Somatic memory is unique to ES cells that have been methylated

a. iPS cells must erase all methylation marks to revert to pluripotency

18


• Methylation of cytosines only occurs when they are followed by G.

T

19

• DNA methylation can lead to accidental expression of inappropriate genes.

F

20

• MeCP2 directly binds methylated Cs and recruits histone deaceytlase, methyltransferase and Dnmt3.

T

21

Chromosomes are most highly condensed and visible during metaphase.

T

22

• Genes expressed in stem cells do not play a role in cell proliferation or housekeeping.

F

23

• A Deletion of a small region of the long arm of chromosome 15 can lead to Prader-willi syndrome when inherited from the egg and Angelman syndrome when inherited from the sperm.

F

24

What doesn’t have a role in allowing epigenetic changes to be heritable?
a. The passive process of DNA replication
b. TET proteins can actively reverse methylation
c. DNMT1 recognises hemi-methylated DNA and methylates the non-methylated strand
d. TET proteins only de-methylate DNA at restricted points during development




a. The passive process of DNA replication (reversibility)

25

How can a cancer cell differ to a normal cell in its DNA methylation patterns?
a. CpG islands undergo extensive de-methylation
b. The repetitive elements are methylated
c. There can be genome-wide hypo-methylation at CpG laden promoters
d. Hyper-methylation can occur at CpG islands and imprint control regions

d. Hyper-methylation can occur at CpG islands and imprint control regions

26

What is the significance of CpG island hyper-methylation?
a. DNA methylation is an alternative to genetic mutation that can silence oncogenes to encourage tumour formation
b. When it occurs at imprint control regions, a loss of imprinting and overexpression of imprinted growth control genes can occur
c. The same CGIs are hyper-methylated in all tumour types which aids diagnosis
d. The methylation pattern is easily distinguished from that which occurs during the natural aging process

b. When it occurs at imprint control regions, a loss of imprinting and overexpression of imprinted growth control genes can occur

27

Which is a well-known example of CGI methylation of a single gene resulting in cancer?
a. BRCA1 and colorectal cancer
b. MGMT and gliomas
c. MLH1 and retinoblastoma
d. RB and breast cancer

b. MGMT and gliomas

28

What is untrue about using hyper-methylated genes as biomarkers?
a. They can be used as biomarkers because CGI are usually un-methylated
b. They can be used to discriminate tumour from normal tissue for diagnosis
c. They can influence treatment strategy
d. They can only be used as biomarkers for imprint control regions as CGI are usually methylated

d. They can only be used as biomarkers for imprint control regions as CGI are usually methylated

29

What is a feature of bivalent genes in stem cells?
a. H3K27me3 marks the gene as repressed and is mediated by PRC2
b. RNA pol II is always active
c. The genes are active but poised for an enhancement in expression
d. H3K4me3 marks the gene as repressed and is mediated by MLL

a. H3K27me3 marks the gene as repressed and is mediated by PRC2

30

What is a feature of bivalent genes in cancer stem cells?
a. They are hypo-methylated
b. There is an absence of H3K4me3 and H3K27me3 marks
c. Genes are no longer poised for activation and are instead stably activated
d. RNA pol II is paused at the promoter and bound by PRC2 and MLL

b. There is an absence of H3K4me3 and H3K27me3 marks

31

What is a feature of genome-wide hypo-methylation?
a. When it occurs in CpG poor promoters, oncogenes can be repressed
b. When it occurs in imprint control regions, imprinting can be enhanced
c. Genomic instability can occur when it happens in repeat or intergenic regions
d. It is only seen in some tumours and depends largely on location

c. Genomic instability can occur when it happens in repeat or intergenic regions

32

What is a feature of cancer stem cells?
a. They are often successfully targeted during chemotherapy
b. They are found in homogenous tumours
c. They can self-renew or differentiate like normal stem cells
d. They are not influenced by epigenetic effects

c. They can self-renew or differentiate like normal stem cells

33

What is a consideration of the CSC theory?
a. Whether self-renewal arise in the original stem cell or did the CSC attain it during tumorigenesis
b. CSCs are found in all cancers
c. CSC theory cannot co-exist with genetic heterogeneity and clonal evolution
d. Unlike cancer, the proportion and features of CSCs do not change over time

a. Whether self-renewal arise in the original stem cell or did the CSC attain it during tumorigenesis

34

How does normal and tumour cell differentiation compare?
a. Self-renewal can be imparted on normal stem, progenitor or differentiated cells following genetic or epigenetic changes
b. The stem cell is always the cell of origin for differentiated tumour cells
c. Differentiation is irreversible in normal cells but not tumour cells
d. Differentiated tumour cells still have the capacity to self-renew

d. Differentiated tumour cells still have the capacity to self-renew

35

What encourages the self-renewal of CSCs?
a. DNA is hypo-methylated in cancer rather than poised for activation/repression
b. DNA methylation is less stable because there is up regulation of de-methylating (TET) enzymes
c. DNA methylation makes it more difficult to activate developmental genes and differentiation is discouraged
d. Epigenetic changes enforce differentiation and self-renewal in a reversible manner like genetic changes

c. DNA methylation makes it more difficult to activate developmental genes and differentiation is discouraged

36

• CpG island methylation increases as the tumour advances.


T

37

• Hyper-methylated genes are enriched for genes silenced by polycomb repressive complex 2 in embryonic and adult stem cells.

T

38

• Hypo-methylation of imprint control regions can lead to open chromatin and illegitimate recombination as well as transcriptional activation of repeats and transposition.

F (repeats, intergenic regions)

39

• Tumours driven by tumour suppresser hyper-methylation show enhanced tumorigenesis following the depletion of DNA methylation.

F

40

• Genetic alteration of epigenetic modifiers can lead to epigenetic effects and epigenetic effects can result in genomic instability.

T

41

• The most common drugs that target epigenetic machinery are aimed at chromatin remodelling proteins.

F (DNMT)

42

• Tumour heterogeneity is driven by genetic changes but not epigenetic changes.

F

43

• In CSCs, epigenetic changes cannot impart self-renewal capacities.

F

44

• In CSCs, transmitted epigenetic changes can lead to the maintenance of the stem cell state at the expense of differentiation.

T

45

• Using DNA methyltransferase inhibition to deplete DNA methylation at bivalent genes could be used to remodel the CSC epigenome and treat cancer.

T