TOPIC F: Cancer Flashcards

1
Q

What are the physical characteristics of a cancer cell compared to a normal cell

A
Enlarged nucleus
Changes to cytoskeleton
Loss of specialised features
Little cytoplasm
Evidence of mitosis

No growth constraints (not limited by neighbouring cells or environment)
No physical attachment

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2
Q

What is a carcinoma

A

A cancer arising from epithelial cells of the skin and lining of organs

85% of all cancers

breast, lung, colon cancers

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3
Q

What is a sarcoma

A

Cancers arising from bone, muscle and blood vessels

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4
Q

What is a Lymphoma

A

Cancer arising from lymphoid cells and leukemias from white cells of the bone marrow

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5
Q

Do cancer cells require growth factors

A

No, can have greatly reduced requirement for growth factors

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6
Q

What is the relationship between cancer cells and telomeres

A

Cancer cells have chromosomal aberrations

  • change in no. of chromosomes
  • change in chromosome structure

Telomere shortening regulates how many round of cell division can occur. Cancer cells can ignore telomere shortening and keep dividing

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7
Q

What are the basic transitions of cancer progression

A

A single mutant cell

to a tumour

to metastasis (cancer spreads throughout body)

At least 4-6 mutations to reach the tumour state. process can decades for single mutant cell to proliferate into palpable tumour

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8
Q

What are the 2 types of tumours

A

Benign: look like original tissues. Localised (do not spread). Don’t cause problems unless in confined space (like brain)

Malignant: Do not look like original tissue. Physical changes, spread

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9
Q

Explain metastasis

A

When cancers invade other issues and spread throughout body.

Depends on type of cancer

Takes a lot of energy to proliferate and spread so angiogenesis occurs

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10
Q

Explain angiogenesis

A

The mechanism where tumours direct capillaries to travel into the tumour so it can have nutrients and oxygen for growth.

Angiogenesis can be targeted to stop cancer from growing

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11
Q

What are some of the implications of cancer genetic alteration

A

Increased cell growth

Resistance to apoptosis

Altered tissue invasiveness

Angiogenic proliferation

Ability to escape immune surveillance

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12
Q

What are 2 main causes of cancer

A

DNA damage

Viruses

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13
Q

Explain the types of DNA damage that can lead to cancer

A

Inherited (germ lime errors): every cell in body carries one copy of DNA with defect. 10% of cancers

Acquired (somatic errors): may lead to cancer in that tissue. only cancer cells carry mutation

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14
Q

How can acquired DNA damage leading to cancer be caused

A

Environmental exposure to:

radiation

viruses

bacteria

chemical carcinogenesis

age and diet

UV light

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15
Q

Cancer cells accumulate more and more errors over time. Why does this occur?

A

Ususally DNA repair enzymes can correct but

  • substantial mutations
  • loss of DNA repair enzymes
  • less time for repair mechanism (rapid cell cycle to divide)

can lead to further DNA damage

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16
Q

Explain how viruses can lead to cancer

A

Infectious agents like viruses are causal agents in some cancers.

15% of cancers like nasopharynx, cervical, liver and lymphomas

17
Q

Explain what an oncogene, tumour suppressor gene, mismatch repair gene, and proto-oncogene are.

A

Oncogene: promotes cancer

Tumour suppressor gene: act to prevent cancer

Mismatch repair gene: repair mutated DNA

Proto-oncogene: Normal genes that promote cell growth and division that could become an oncogene

18
Q

What mutations can occur on a proto-oncogene

A

Deletion or point mutation = hyperactivity

Gene amplification = normal protein overproduced

Chromosome rearrangement = changes in regulation

19
Q

Oncogenes are dominant meaning…

A

that one gain-of-function mutation can predispose a cell to cancer as it overrides the rest of cellular function

20
Q

What cell functions are tumour suppressor genes involved in

A

Control cell cycle check points

Induce transcription of regulatory inhibitory genes

Overall, negatively control cell growth

21
Q

What mutation can occur for a tumour suppressor gene

A

Loss of function mutation

Can be inherited or acquired

Both copies of gene must be lost for cancer to develop (two hit hypothesis)

22
Q

Explain the two hit hypothesis

A

Loss of one copy of a tumour suppressor gene causes a slight cell progression advantage

Loss of both copies causes complete inactivation, significant growth advantage and predisposition to cancer

23
Q

What is retinoblastoma

A

Rare childhood tumour of the retina (neural precursor cells of retina)

Caused by non-function retinoblastoma (Rb) tumour suppressor gene

2 forms: hereditary and sporadic

Both copies of gene must be lost

24
Q

Explain the 2 types of retinoblastoma

A

Hereditary: young age, tumours in both eyes, mutant Rb allele on chromosome 13 in every cell of body

Non-hereditary/sporadic: 1 tumour in 1 eye, later age, mutant only in tumour cells

25
What are the usual cell functions of p53
master regulator of cell death cell cycle arrest senescence cell differentiation apoptosis DNA repair
26
How does p53 cause cell death
Inducing selective gene expression to inhibit cell growth or induce apoptosis stabilising p53 protein leads to increase in p53 levels
27
What are the results of p53 mutation
Chromosomes become fragmented, incorrectly rejoined Successive cell divisions produce largely mutated genome
28
Explain MMR genes roles in cancer and mutation
8 MMR genes including MSH, MLH, PMS Often lost or defective in cancers 2 hit hypothesis
29
What does hereditary cancer motivate
routine screening for cancers genetic counselling
30
What are some of the features of inherited cancer
Several close relatives with common or related cancers 2 family members have the same rare cancer Early age onset Bilateral cancers in paired organs Tumours in 2 different organs
31
What is penetrance
The percentage of individuals with specific genetic defect who will get the disease Varies depending on gene
32
What are some features of inheritance of BRCA 1 and 2 breast cancers
Mutliple early onset cases in family Breast and ovarian cancer history Breast and ovarian cancer in same woman Bilateral breast cancer Ashkenazi jewish heritage Male breast cancer
33
Explain tyrosine kinase receptor as an oncogene
Mutation or over-expression can cause cellular transformation (cancer) as they are involved in activating multiple oncogenes
34
Outline chronic myeloid leukemia (CML)
Leukemic cells have 9:22 translocation causing abnormal tyrosine kinase receptors Arises from single abnormal hematopoietic stem cell Proliferation of immature white blood cells CML cells proliferate unchecked leading to - bone marrow replacement - increased liver size - white blood cell increase
35
What is the Philadelphia chromosome
Shortened chromosome 22 End of chromosome 9 (containing abnormal tyrosine kinase) dused with B cell receptor (BCR) on chromosome 22 Fusion of bcr-abl produces a fusion protein which increases tyrosine kinase compared to normal and causes leukemia
36
How can CML be diagnosed
demonstration of chromosomal translocation by standard cytogenetics, FISH or PCR
37
What are the 3 main types of cancer treatment
Chemotherapy: kills rapdily dividing cells but also normal cells Surgery: Cut cancer out, not always possible Targeted therapies: find molecular cause and design therapies
38
For cancers with TKR signalling like CML what are some treatment strategies
ATP - competitive inhibitors: stop TKR binding to ATP, blocking activity Other anti-TK drugs: Antibodies against receptor or ligands, blocking activation Antibodies against RTK or lignads: Block ligand binding, receptor internalisation Anti-angiogenics: TK inhibitors as a target for anti-angiogenesis