Cancer 2 Flashcards

1
Q

What is cancer?

A

Broad complex group of diseases characterised by uncontrollable growth of cells which do not die

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2
Q

Why do cancers tend to occur in older patients?

A

There is more time for accumulation of genetic changes

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3
Q

Name 6 major hallmarks of cancer

A
  1. Sustaining proliferative signalling
  2. Evading growth suppressors
  3. Activating invasion and metastasis
  4. Enabling replicative immortality
  5. Inducing angiogenesis
  6. Resisting cell death
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4
Q

Name 4 proteins in cytoplasm which have cell cycle control

A
  1. Cyclins
  2. Cyclin dependent kinases (CDKs)
  3. Cyclin dependent kinase inhibitors (CKIs)
  4. Anaphase promoting complex (APC)
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5
Q

Describe 3 cytoplasm proteins which are affected in a tumour cell

A
  • Over expression of cyclins
  • Over expression of CDKs
  • Deactivation of CKIs
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6
Q

Describe a major characteristic of tumour cells with regards to cell division but unrelated to the major cytoplasm proteins

A

Abnormality of checkpoints

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7
Q

What are 2 genes which cause sustained proliferative signalling?

A
  1. Activation of oncogene

2. Inhibition of tumour suppressor genes

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8
Q

Describe oncogenes

A
  • Dominant

- Encourage cell division

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9
Q

Name 3 types of hyper activation of genes which promote growth

A
  1. Gene fusions / translocations (BCR-Abl)
  2. Point mutations (KRAS)
  3. Amplification (HER2)
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10
Q

Describe tumour suppressor genes

A
  • Recessive
  • Keep cell growth under check
  • Can repair damage or stop cell dividing
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11
Q

Name 4 ways tumour suppressor genes can be altered

A
  1. Point mutations
  2. Deletion of regions of chromosomes
  3. Loss of heterozygosity
  4. Altered methylation of promoter
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12
Q

Describe familial cancer syndromes

A
  • Recessive at a cellular level but dominant with regard to cancer risk
  • Point mutation knocks out recessive gene
  • Only one more gene must be knocked out instead of 2
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13
Q

What is Li-Fraumeni Syndrome caused by?

A

Mutation in p53

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14
Q

Describe the familial form of retinoblastoma

A
  • Child inherits one mutant copy of Rb1 gene
  • Disease occurs earlier
  • Higher probability of disease occurring in 2 eyes
  • Tumour may be multi-focal and bilateral
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15
Q

Describe the sporadic form of retinoblastoma

A
  • Mutation has to occur in both copies of Rb1 gene
  • Unlikely for 2 mutations in more than one cell
  • Tumour occur later in life
  • Tumours are likely to be unilateral
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16
Q

Name 4 stresses on a cell which normally causes p53 activation

A
  1. DNA damage
  2. Hypoxia
  3. Heat / cold shock
  4. Mitotic spindle damage
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17
Q

Name 4 outcomes triggered in a normal cell by p53 activation

A
  1. Cell cycle arrest
  2. DNA repair
  3. Apoptosis
  4. Senescence
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18
Q

How does HPV affect p53 gene?

A

HPV encodes a protein which binds to and inactivates p53

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19
Q

How do cancers tend to activate invasion and metastasis?

A

Cell-Extracellular matrix interactions are altered

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20
Q

Name 4 ways cell-extracellular matrix interactions are altered

A
  1. Changes in structural proteins (integrins)
  2. Up regulation of enzymes for tissue break down (MMPs)
  3. Altered expression of chemokines (IL8)
  4. Altered growth factor expression (FGFs)
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21
Q

What is metastasis?

A

Process by which cancer cells spread to other parts of the body

22
Q

Name 3 routes of metastasis

A
  1. Lymphatic
  2. Haematogenous
  3. Transcoelomic
23
Q

What tumours tend to metastasise in a haematogenous fashion?

24
Q

What tumours tend to metastasise in a transcoelomic fashion?

A

Ovarian tumours can spread transperitoneally to liver

25
Describe the multi step process of metastasis
- Primary tumour proliferation - Invasion of neovasculature - Embolism and transport - Adherence to vessel wall - Extravasation - Establishment of a microenvironment - Metastasis
26
Name 4 common sites of metastasis for breast cancer
1. Bone 2. Brain 3. Liver 4. Lung
27
Name 3 common sites of metastasis for colorectal cancer
1. Liver 2. Lung 3. Peritoneum
28
Name 5 common sites of metastasis for lung cancer
1. Adrenal gland 2. Bone 3. Brain 4. Liver 5. Other lung
29
Name 4 common sites of metastasis for prostate cancer
1. Adrenal gland 2. Bone 3. Liver 4. Lung
30
Describe normal replicative senescence
- Cells have finite lifespan and limited ability to replicate - Due to telomere shortening
31
Describe how cancerous cells enable replicative immortality
- Inactivation of pRb / p53 extends lifespan 30 doublings - Rare mutations lead to immortalization - Activation of telomerase
32
Describe induction of angiogenesis by cancerous cells
- Pro-angiogenic factors activated in tumours - Signal endothelial cell proliferation - Growth of blood vessels
33
Name 3 pro angiogenic factors
1. VEGF 2. FGF1 3. FGF2
34
What is apoptosis?
Programmed cell death
35
Name 2 pro survival factors activated in tumours
1. Bcl-2 | 2. Cflip
36
Name 5 causes of cancer
1. Lifestyle (tobacco / alcohol / diet) 2. Infections 3. Radiation exposure 4. Age 5. Genetics
37
Name 4 molecular mechanisms driving carcinogenesis
1. Mutations 2. Chromosomal abnormalities 3. Gene amplifications 4. Altered gene expression
38
Name 3 types of point mutations
1. Silent 2. Nonsense 3. Missense
39
What is a point mutation?
Single change in a base
40
What is a silent point mutation?
Single change in the base but the protein is unchanged
41
What is a nonsense mutation?
Single change in the base where there is no coded protein for the new sequence
42
What is a missense mutation?
Single change in the base where the protein produced is different
43
Describe 2 examples of point mutations
1. Ras family (codes a small GTPase involved in transmitting signals) 2. KIT gene (codes a transmembrane tyrosine kinase)
44
Name 2 ways deletions can occur
1. Loss of single base | 2. Loss of large regions of chromosome
45
Describe 2 ways translocation can affect the body
1. Production of novel fusion proteins (Bcr-Abl) | 2. Juxtaposition to strong promoter upstream (cMyc)
46
Describe the Philadelphia chromosome
- Chronic Myeloid Leukaemia is characterised by Philadelphia chromosome - Translocation of portion of q arm of chromosome 22 to q arm of chromosome 9 - Creates fusion gene juxtapositioning the Abl1 gene on chromosome 9 to part of BCR gene on chromosome 22
47
What is gene amplification?
Increased copy number of genes which may be amplified multiple times (HER2 in breast cancer)
48
Name 2 epigenetic changes which alter gene expression
1. DNA methylation | 2. Histone modification
49
Describe an example of DNA methylation leading to altered gene expression
- p16 methylation - Acetylation opens up chromatin - Methylation of chromatin can cause transcriptional activation or repression
50
Name 4 emerging hall marks of cancer
1. Avoiding immune destruction 2. Tumour promoting inflammation 3. Genome instability and mutation 4. Deregulating cellular energetics
51
Name 3 "E's" of immunoediting
1. Elimination 2. Escape 3. Equilibrium