L1.1 cancer epigenetic

Question 1

what are the four stages of cancer progression

Answer 1

initiation, promotion, progression and metastasis

Question 2

what is initiation of cancer

Answer 2

the change of mutations arising spontaneously or induced by exposure to an agent.

Question 3

what happens the promotion stage of cancer progression

Answer 3

cells actively proliferating accumulate

Question 4

what happens during the progression stage of cancer

Answer 4

genetic and phenotypic changes occur are fast increase in tumour size

Question 5

what is metastasis

Answer 5

spread of cancer cells to other parts of the body through blood or lymph

Question 6

what is the definition of cancer

Answer 6

Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the body

Question 7

what are the 10 hallmarks of cancer

Answer 7

evading growth suppressors

activating invasion and metastasis

sustained proliferative signalling

avoiding immune destruction

tumour promoting inflammation

genome instability and mutation

inducing angiogenesis

enabling replicative immortality

deregulating cellular energetics

resisting cell death

Question 8

what are some of the DNA methylation changes detected in cancer cells?

Answer 8

1. gene specific hypo- and hyper-methylation
2. Global hypomethylation across the genome
3. Increase incidence of mutations

Question 9

repeat sequences containing transposable elements are hypo or hyper methylated?

Answer 9

hypomethylated

Question 10

what are transposable elements?

Answer 10

unstable DNA which are heavily methylated and mobile can cause genome instability

Question 11

what type of cells are stem cells

Answer 11

pluripotent

Question 12

what is a pluripotent cell

Answer 12

undifferentiated and can differentiate into different cell linages

Question 13

what are the characteristics of cancer cells within a tumour

Answer 13

undifferentiated and have capacity to self-renewal.

resistant to chemo

Question 14

which two ways can cancer stem cells originate by?

Answer 14

1. De-differentiation of somatic or differentiated cancer cells
2. Mutations and epigenetic changes in normal stem cells or progenitor cells can lead to their formation.

Question 15

what are totipotent stem cells

Answer 15

give rise to hundreds of cells found in the embryo and placenta

Question 16

what are multipoint stem cells

Answer 16

can develop into a limited number of cell types within a linage

Question 17

epigenetic abmormailities provide cancer cells with their key phenotypic characterstics such as

Answer 17

• Enhanced plasticity
• Loss of cell identify
• Differentiation and ability to self-renew

Question 18

epigenetic abnormalities are associated with…

Answer 18

the development and progression of cancer

Question 19

how can epigenetics be used in detection and diagnosis

Answer 19

detection of hypomethylated genes in biological fluid is a biomarker for early diagnosis

Question 20

how can epigenetics be used in prognosis

Answer 20

whole genome wide methylation can be indicators of prognosis

Question 21

how can epigenetics be used in prediction

Answer 21

hypermethylation of some genes has been identified as an independent predictive factor

Question 22

how can epigenetics be used in follow up for leukaemia

Answer 22

in Leukaemia cells p15 methylation initiates proliferation so if in follow up this gene is methylated it indicates cancer recurrence.

Question 23

what are the negative effects of chemotherapy

Answer 23

resistant to treatment, negative quality of life, toxicity, development of secondary malignancies.

Question 24

epigenetic drugs are referred to as …

Answer 24

small molecule inhibitors or epidrugs

Question 25

why do drugs target epigenetic machinery

Answer 25

1. It is well-established that epigenetic dysregulation has a key role in origin and progression of all cancers
2. Unlike mutations epigenetic modifications are reversable

Question 26

small molecule inhibitors are designed to do what?

Answer 26

target enzymatic epigenetic regulators which place or remove an epigenetic tag

Question 27

what is the aim of epigenetic drugs

Answer 27

to activate tumour suppress genes, deactivate oncogenes, prevent proliferation and trigger apoptosis in cancer cells by targeting and altering the epigenome of the cancer cell.

Question 28

what do DNMT inhibitors do

Answer 28

prevent hypermethylation of genes, stimulates reprogramming, results in cell death

Question 29

what are the two types of DNMT inhibitors

Answer 29

Nucleoside analogs

Non-nucleoside DNMTi

Question 30

what are Nucleoside analogs

Answer 30

replication dependent because it is incorporated into DNA/RNA synthesis

Question 31

what are Non-nucleoside DNMTi

Answer 31

small molecules that are not incorporated into DNA to inhibit function of enzymes. these block catalytic sites of the enzyme

Question 32

what are HDAC inhibitors. And examples

Answer 32

small molecule target and inhibit the activity of histonedeacetyltransferase which makes DNA less accessible for transcription which suppresses the genes. Results In apoptosis

Vorinostat and romidepsin

Question 33

Describe what DNMT is and what is the role of DMNTi and examples

Answer 33

DMNTi is an inhibitor which inhibits the enzymes that methylate DNA to prevent tumour suppressor genes from being methylated and suppressed.

Decitabine and vidaza