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Cancer Genetics Flashcards

1
Q

What is a cancer?

A

An abnormal growth of cels which tend to proliferate in an uncontrolled manner, and in some cases, to metastasize

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2
Q

What causes cancer cells to behave abnormally?

A

Changes in the DNA sequence of key genes which are known as cancer genes

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3
Q

What are the two causes for mutations in DNA?

A

Tumour supressor genes being silenced or oncogenes being over-expressed

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4
Q

What are oncogenes?

A

Genes which stimulate the cell cycle

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5
Q

What are tumour supressor genes?

A

Genes which halt the cell cycle

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6
Q

What are the 6 hallmarks of cancer?

A

SAAIIL

Self Sufficiency
Avoid apoptosis
Angiogenesis
Invasion and metastasis
Insensitive to anti-growth signals
Limitless division
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7
Q

What is a benign tumour?

A

A mass of well-differentiated cells that grows slowly, is capsulated and lacks the ability to invade neighbouring tissue or metastasise

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8
Q

What is a malignant tumour?

A

A tumour which is not self limited in growth, cells are poorly differentiated and capable of invading into adjacent tissues = metastasis

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9
Q

What four things can cause cancer?

A
  • Radiation
  • Chemicals
  • Viruses
  • Hereditary alteration in genes which make a person more susceptible to cancer
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10
Q

What is the difference between benign and malignant tumours?

A

benign grow slow, malignant fast
benign is well differentiated, malignant is not
benign is capsulated, malignant is not
benign cannot metastasize or invade neighbouring tissue, malignant can

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11
Q

What type of cancers have epithelial tissue origin?

A

Carcinomas

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12
Q

What are common types of carcinomas?

A

Lung, breast and colon cancer`

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13
Q

What is the name given to cancers which arise from cells found int he supporting tissues of the body?

A

Sarcomas

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14
Q

What are cancers that arise in lymph nodes and tissues of the body’s immune system called?

A

Lymphomas

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15
Q

What are cancers that arise from immature blood cells that grow in the bone marrow called?

A

Leukaemia

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16
Q

What is the most common cancer in children?

A

Acute lymphoblastic leukaemia

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17
Q

What type of mutation can be passed on to off-spring?

A

Germline mutations can be passed on

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18
Q

What type of mutatins cannt be passed on to off-spring?

A

Somatic mutations

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19
Q

A gene change in which cells cause germline mutations?

A

Reproductive cells

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20
Q

What are somatic mutations also known as?

A

Acquired or sporadic mutations

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21
Q

What are the seven types of mutations?

A 
deletions
insertions
aneuploidy
inversions
translocations
single base mutations
chromosome instability
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22
Q

What is a deletion mutation?

A

When one or more nucleotide is removed from the DNA

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23
Q

what is a duplication mutation?

A

When one or more copies of a gene or region of a chromosome are made

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24
Q

What is an inversion?

A

Reversing the orientation of a chromosomal segment

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25
What is a driver mutation?
A mutation which contributes to cancer growth
26
What is a passenger mutation?
A mutation which occurs during cancer growth
27
What type of studies can help identify cancer germline mutations?
Positional cloning linkage studies through gene mapping and gene indentification
28
What are the three types of point mutations?
Silent, non-sense and mis-sense
29
What affect does UV radiation have on the DNA?
forms covalent bonds between two adjacent pyrimidines (C and T) in the DNA molecule which causes cross linking, resulting in the formation of a dimer
30
What happens in the dimer formed due to UV radiation is not repaired?
Most DNA polymerases will insert 2 adenine opposite the dimer, resulting in a mutation
31
What does oncogene issues generally result in?
An increase in some form of protein activity, or a loss of regulation
32
Describe the process multistep carcinogenesis?
1. begins with mutation in tumour supressor gene which therefore allows excessive cell proliferation 2. proliferating cells tend to acquire additional mutations 3. overtime the accumulated damage can yield a malignant, metastatic tumour
33
what type of protein is RAS?
A GTPase
34
What state is RAS in when GDP is bound?
It is inactive
35
Does Ras bind GDP or GTP with a higher affinity?
GTP
36
When Ras binds GTP, what state is Ras then in?
Active state
37
How does GAP ensure that Ras is not always active?
GTPase Activating protein hydrolyses the GTP into GDP so Ras is turned off
38
What happens when RAS is constantly stuck in the active form?
the cell extensively proliferates causing cancer as RAS controls a lot of cellular signalling pathways
39
What is the two hit hypothesis? and how does it relate to mutations to tumour supressor genes?
The two hit hypothesis states that both alleles that code for a particular protein must be affected before an affect is manifested. Most mutations to tumour supressor genes are recessive, meaning in order for a particular cell to become cancerous, both of the alleles for the cells tumour supressor genes must be mutated
40
What do mutations in tumour supressor genes result in?
A loss of function, as they can no longer stop the cell from proliferating uncontrollably
41
what is the first event in the two hit hypothesis?
AN inherited mutation - however inheriting one germ line copy of the damaged gene is not sufficient
42
What is the second hit in the two hit hypothesis?
When the second (good) copy in the gene pair is mutated - causing cancer
43
What is p53?
a tumour supressor protein that is encoded by the TP53 gene
44
Loss of the TP52 gene gene due to mutation or deletion occurs in what percentage of human cancers?
>50%
45
What is Li-Fraumeni syndrome?
an inherited condition which is characterised by an increased risk for certain types of cancers
46
What mutagens can cause damage to the TP53 gene?
Chemicals, radiation or viruses
47
What is a retinoblastoma?
Cancer of the retina
48
What does Rb protein do?
Prevents excessive cell growth by inhibiting cell cycle progression until a cell has made all the necessary checks in the G1 phase
49
What transcription factor does retinoblastoma protein bind?
E2F
50
What has to happen to the Rb for the E2F to be released?
Rb has to be phosphorylated - this leads to transcription
51
How do cancer cells evade the immune response?
activation of the checkpoint pathways such as PD-1 send negative signals to the cell to stop if from attacking the tumour cell
52
how does nivolumab work?
binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2,so the negative signals cannot be sent anymore
53
What is positional cloning?
A tab technique used to locate the position of a disease associated gene along a chromosome
54
Which type of mutation tends to cause clonal expansions?
Driver mutations
55
What is the life-time risk of developoing cancer in a particular tissues correlated with?
How often the stem cells in that tissue divide
56
How are most cancer causing mutations involving oncogenes acquired?
Chromosome rearrangements and gene duplications
57
What does the translocation between chromosome 9 and 22 result in?
The formation of the ABL-BCR gene which makes elevated tyrosine kinase activity - leads to more cell proliferation
58
What is a proto-oncogene?
Genes that cause oncogenes to be turned on
59
What condition is cuased by a mutation in the RET gene?
Multiple Endocrine Neoplasia Type 2 (MEN2)
60
What type of cancer do people with multiple endocrine neoplasia type 2 develop?
a form of thyroid cancer called medullary cancer of the thyroid
61
What is the nature of most loss-of-function mutations that occur in tumour suppresor genes?
Recessive
62
What three things make cancer cells genetically unstable?
Unable to stop the cell cycle to allow time for repair Unable to carry out efficient repair Unable to undergo apoptosis
63
What do DNA repair genes do?
Code for proteins whose normal function is to correct errors which arise when cells duplicate prior to cell division
64
What factors is the rate of DNA repair dependant on?
Cell type, age of cell and extracellular environment
65
After a cell has accumulated alot of DNA damage, what are the three states it can enter into
Dormancy Apoptosis / programmed cell death Unregulated cell division = cancer
66
What can mutations in DNA repair genes lead to?
Failure to repair which in turn allows mutations to accumulate `
67
How do viruses cause DNA damage?
Insert their genomes into the DNA of the host cell, which can disrupt important regulatory genes
68
What does the E7 protein from HPV do to promote cancer?
Binds to Rb to promote its degradation which allows cells to divide faster and
69
What are three viruses associated with cancer?
Papillomavirus Hepatitis Virus Epstein-Barr Virus
70
What has lead to the discovery of many common low risk variants for different cancers in recent years?
Genome wide association studies
71
What does the two-hit hypothesis predict?
That the chances for a cell with a germ-line mutation to get a second hit ie a somatic mutation is much higher than the chances of a non-carrier to get two hits in the same cell

GENETICS (9 decks)

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