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POM > cancer genetic > Flashcards

cancer genetic Flashcards

1
Q
  • What do all cancers result from?

- What type of disease are all cancers?

A

Result from changes in the DNA sequences of our genome (these changes occur throughout life because the genome within our cells has been exposed to mutagens like UV radiation)

Genetic diseases
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2
Q
  • A mutation in what type of gene causes cancer?

- List some factors that can cause cancer

A

Cancer gene (mutation alters the function of cancer genes)

Chemicals (e.g. from smoking) and radiation from environment can damage genes 
Viruses can introduce their own genes into cells (exogenous factors)
Heredity, alteration in genes that make a person more susceptible to cancer
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3
Q
  • What is a benign tumour and give a common example?
A

Mass of well-differentiated cells that grow slowly, is capsulated and lacks the ability to invade neighbouring tissue or metastasise
e.g. skin moles or uterine fibroids

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4
Q
  • What is a malignant tumour?
A

Cells are poorly differentiated and capable of invading into adjacent tissues and may be capable of spreading to distant tissues (metastases)

not self limited in its growth (evades apoptosis, and can produce new blood vessels

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5
Q
  • How can a malignancy be detected?
A

Doctor can take sample of cells via biopsy

Biopsy is analysed under a microscope by a pathologist 

If sample shows multiple cells with atypical morphology it may be categorised as malignant
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6
Q
  • What do cancer cells look like under a microscope?
A

Abnormally large shaped nuclei

Disorganised arrangement 

Cytoplasm may also display abnormality such as invaginations 

Large nucleus to cytoplasm ratio
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7
Q
  • What forms the structural basis of the nuclear pore?

- Why does an increase in the number of nuclear pores lead to in advanced cancer?

A

Nuclearporins

Abnormal influx of beta-cotinine onto the nucleus 
(beta-cotinine - important transcription factor that is often mutated in colorectal cancer)
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8
Q
  • What are lymphomas?

- What are leukaemia’s?

A

Cancers of the immune system that arise in lymph nodes and tissues of the body’s immune system

Cancers of the immature blood cells that grow in the bone marrow and tend to accumulate in large numbers in the bloodstream
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9
Q
  • What are carcinomas?

- What are sarcomas?

A

Most common types of cancer arising from cells that cover external and internal body surfaces. Lung, breast and colon are the most frequent cancers of this type (epithelial)

Cancers arising from cells found in the supporting tissues of the body such as the bone, cartilage, fat, connective tissue and muscle
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10
Q
  • What type of cancer accounts for the most number of cancer death in the UK?
  • What are the most common cancers in young people?
A

Lung cancer

Leukaemia, ALL, AML, germ cell tumours (testicular cancer), brain tumours (glioma and medulloblastoma)
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11
Q
  • What are the 6 hallmarks of cancer?
A

Evading apoptosis - Produce IGF survival factors

Insensitivity to anti-growth signals - Lose retinoblastoma suppressor

Sustained angiogenesis - Produce VEGF inducer

Limitless replicative potential - Turn on telomerase

Tissue invasion and metastasis - Inactivate E-cadherin

Self-sufficiency in growth signals - Activate H-Ras oncogene
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12
Q
  • What does the lifetime risk of developing cancer in a particular tissue correlate with?
  • What are the 4 emerging cancer hallmarks?
A

How often stem cells divide in that tissue

Chromosomal instability
Evading the immune system 
Deregulating cellular energetics
Tumour promoting inflammation
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13
Q
  • What are somatic cells?

- What are the difference between germline and somatic mutations?

A

All cells that form building blocks of the body other than gametes

Germline are present in egg or sperm whereas somatic occur in non-germline tissues
Germline is heritable and rare whereas somatic are non-heritable and very common
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14
Q
  • Which cell type mutation is the most common cause of cancer?
  • Why are somatic mutations non-heritable?
A

Somatic mutation

Because they only occur in somatic cells and not gametes
Only germline mutation in gametes can be passed onto offspring
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15
Q
  • Name a mutation in which gene leads to an increased risk for breast cancer as a part of hereditary breast ovarian cancer syndrome?
  • List the different types of mutation
A

BRCA-1 gene

Deletions
Duplications 
Inversions 
Translocations 
Single base mutations (point mutations  - silent, nonsense, missense)
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16
Q
  • What 3 steps can multi-step carcinogenesis be divided into?
A

Initiation - results from an irreversible genetic alteration. Most likely it is a simple mutation in a tumour suppressor gene

Promotion - excessive cell proliferation and subsequent accumulation of other mutations involving DNA repair genes or tumour suppressors (p53) or growth related genes (K-ras)

Progression - tumour becomes a carcinoma due to accumulated damage and progress to metastasise in an event
17
Q
  • What does DNA damage from UV radiation lead to?

- What is the signature mutation of UV light?

A

Formation of covalent bonds between 2 adjacent pyrimidines (CC,TC,CT or TT) in the DNA molecules

C to T transition dipyrimidine context
18
Q
  • What does ‘passenger mutation’ refer to?

- What does ‘driver mutation’ refer to?

A

Mutations that provide no proliferative benefit, occur during cancer growth

Confer a fitness advantage to somatic cells in their microenvironment, contribute to cancer growth
19
Q
  • What are oncogenes defined as in terms of driver mutations?
  • What are tumour suppressor genes defined as in terms of ‘driver mutations’?
A

Cancer genes in which driver mutations are activating or resulting in new functions

Cancer genes in which driver mutations are inactivating the function
20
Q
  • When may a passenger mutation be associated with clonal expansion?
  • Are most cancer causing mutations involving oncogenes acquired or inherited?
A

When they occur in the same genomes, carrying a driver mutation

Acquired (mainly in somatic cells and very rarely inherited through the germline)
21
Q
  • What specific chromosomal abnormality is associated with CML?
A

(Reciprocal) Translocation between chromosome 9 and 22, which create an elongated chromosome 9 and truncated chromosome 22

Fuses BCR and ABL
22
Q
  • What is Myc?

- What cellular processes does Ras protein control?

A

Potential transcription factor acting as a proto-oncogene

Growth, migration, adhesion, cytoskeleton integrity, survival and differentiation
23
Q
  • When Ras protein is mutated what happens?
  • What is the specific Ras oncogene that is mutated?
  • What is the activity of Ras governed by?
A

Cell proliferation is disrupted and the cell starts to divide in an uncontrolled manner

k-Ras 

Its binding to GTP in the active state

Or to GDP in its inactive state
24
Q
  • What is a tumour suppressor gene (TSG)?

- What happens when a TSG is mutated?

A

A gene that regulates a cell during cell division and replication- when active it inhibits cell replication

Results in a loss or reduction of its function and in combination with other genetic mutation or with the loss of a second allele, it could allow the cells to grow abnormally

Loss of functions of these genes is often recessive
25
Q
  • What was the first tumour suppressor protein discovered?
  • Give one function of retinoblastoma and explain how it carries out this function
  • What phosphorylates retinoblastoma leading to its inactivation?
A

Retinoblastoma protein Rb, in human retinoblastoma (cancer of the retina)

Prevents excessive cell growth by inhibiting cell cycle progression until a cell has made all checks necessary in G1 phase

Cyclin dependant kinase

26
Q
  • Explain the two-hit hypothesis
A

In the first event there is an inherited mutation, however inheriting one germline copy of a damaged gene present in every cell in the body is not sufficient to enable this cancer to develop

A second hit to the good copy in the gene pair could occur somatically, producing cancer
27
Q
  • Retinoblastoma belong to the pocket protein family whose members have a pocket in the structure for the functional binding of other proteins. What binds to the pocket in retinoblastoma?
A

E2F (important transcription factor essential for activation of the transcription programme of a cell moving onto S phase from G1)

28
Q
  • What gene encodes the TSG p53?

- In what syndrome can abnormality of the p53 gene be inherited?

A

TP53

Li-Fraumeni syndrome; abnormality can increase the risk of developing various types of cancer
29
Q
  • Explain the roles of BRCA1 and BRCA2 in DNA repair?
A

BRCA1 is phosphorylated by ATM and CHK2 in response to breaks in double-stranded DNA.

BRCA1 binds to BRCA2 which interacts with RAD51 to form a complex which is involved in DNA repair
30
Q
  • Which HPV proteins confer a selective growth advantage to the host cells by interfering with the normal function of retinoblastoma and p53?
A

E6 and E7

31
Q
  • What 3 possible states can a cell that has accumulated a large amount of DNA, or one that no longer effectively repairs damage incurred to its DNA enter into?
A

An irreversible state of dormancy

Cell suicide, AKA apoptosis (programmed cell death)

Unregulated cell division, which can lead to the formation of a tumour that is cancerous

POM (47 decks)

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