L9 oncogenes and tumour suppressor genes Flashcards Preview

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Flashcards in L9 oncogenes and tumour suppressor genes Deck (29)
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1
Q

normal cells

A

socially responsible for the survival of the whole organism

divide, move, differentiate and die when appropriate

2
Q

cancer cells

A

selfish

accumulate mutations, divide uncontrollably and move throughout the body at the expense of neighbouring cells and the whole organism

3
Q

cancer is caused by genetic (or epigenetic changes)

A

caused by genetic changes that affect gene expression/function

genetic changes caused by:

  1. mutations
  2. chromosomal abnormalities
  3. introduction of genes by viruses
4
Q

Categories of cancer

A

see onenote

  1. carcinoma
  2. sarcoma
  3. melanoma
  4. leukemia
  5. lymphoma
  6. retinoblastoma, glioblastoma, medulloblastoma, neuroblastoma
5
Q

cancer

A

disease featuring abnormal and improperly controlled cell division resulting in invasive growths, tumours that may spread throughout the body

strongly related to age

long exposure to mutagens increases incidence

6
Q

benign vs malignant tumours

A

benign

  • non cancerous
  • generally stop growing, do not spread to other parts of the body and do not create new tumours

malignant

  • cancerous
  • can invade healthy tissues, interfere with body functions, can draw in blood vessels to get nutrients and oxygen for more growth
  • can spread to other parts of the body and create new tumours
7
Q

Hallmarks of cancer

A
  1. sustaining proliferative signalling
  2. evading growth suppressors
  3. activating invasion and metastasis
  4. enabling replicative immortality
  5. inducing angiogensis
  6. resisting cell death
8
Q

Tumorigenesis

A
  1. resisting cell death
  2. sustaining proliferative signalling
  3. evading growth suppressors
9
Q

Metastasis

A

the spread of cancer cells from one site in the body to another site

Tubes throughout your body, if tumour can get into transport system, can get throughout your body

  1. inducing angiogenesis
  2. activating invasion and metastasis
10
Q

Tumour development

A

see onenote diagram

cancer occurs by cells acquiring multiple mutations over a long period of time that gradually transform them into cancer cells

11
Q

Tumorigenesis is a balance between proliferation and cell death

A

increase proliferation/decrease apoptosis => tumour

apoptosis: programmed cell death

cell proliferation: increase in cell number by division

senescence: cell which is still alive but not actively dividing, in a state of arrest which is normally irreversible

12
Q

Oncogene

A

see onenote

a gene that, when mutated/expressed at high levels helps turn a normal cell into a cancer cell (transformation)

normal form - proto-oncogene, involves in cel proliferation, growth, invasiveness e.g. Ras, PI3K, twist

13
Q

Tumour suppressor gene

A

see onenote

a gene that acts to prevent a normal cell from turning into a cancer cell

  • limit cell proliferation, promoting cell death, preventing metastasis
  • knudson two hit theory
  • anti-oncogenes
  • p53, pten, Rb
14
Q

Normal cellular roles of proto-oncogenes and tumour suppressor genes

A

see onenote

15
Q

oncogenes vs tumour suppressor genes

A

see onenote

16
Q

Possible ways by which proto-oncogenes can be activated

A

see onenote

17
Q

Knudson “two hit” model for the inactivation of tumour suppressor genes

A

see onenote slides

Knudson “two-hit” model

  • One copy knocked down, wait for the other copy to be knocked out => loss of function
  • Loss of first copy could be random or inherited

Loss of second copy - loss of heterozygosity

18
Q

Inactivation of tumour suppressor genes can involve both genetic/epigenetic changes

A

see onenote

19
Q

sequencing of many cancers reveal different pattern of mutations in oncogenes vs TSGs

A

see onenote

Can tell if its oncogene or tumour suppressor from looking at amount and spread of mutations

TSGs most mutations are truncating

oncogenes mutations found repeatedly at key aa positions, truncating mutations are rare

20
Q

Burkitt’s lymphoma

A

see onenote slides

aggressive cancer of the lymphatic system involving over proliferation of B lymphocytes

protooncogenic translocation to a region of high transcriptional activity

  • reciprocal translocation between chromosome 8 and 14
  • Myc protooncogene gets put next to powerful enhancer => expressed at high level, drive cell growth and proliferation pathway at high levels
21
Q

Increased myc expression causes cell proliferation

A

see onenote

Myc is a TF, promotes cell growth and proliferation by controlling expression of target genes in response to many signalling pathways

excessive myc => hyper-proliferation of lymphocytes

22
Q

Chronic myeloid leukaemia (CML)

A

cancer in which the bone produces too many granulocytes (a type of white blood cell)

  • reduced number of healthy white blood cells, RBC and platelets
  • leads to increased infection, anaemia and easy bleeding
23
Q

Possible ways proto-oncogene can be activated - gene fusion event creating an altered function protein

A

see onenote

24
Q

CML caused by reciprocal chromosomal translocation

A

see onenote

reciprocal translation between chromosomes 9 and 22
- results in philadelphia chromosome and a fusion between c-abl gene which encodes kinase and Bcr genes => increases kinase activity

25
Q

Bcr-Abl oncogene is constitutively active

A

see onenote

constitutively active kinase => misregulation of cellular signalling pathway that it mediates

26
Q

Retinoblastoma (Rb)

A

regulates the cell cycle

rare childhood tumour which develops from neural progenitor cells in the immature retina

27
Q

Rb protein inhibits the cell cycle

A

see onenote slides

Without Rb, E2F is costanlty turned on

28
Q

p53

A

see onenote

tumour suppressor, “guardian of the genome”

homozygous loss of p53 found in many carcinomas

Almost every cancer has lost p53 function

P53 turns on most anti-cancer mechanisms

29
Q

Li-Fraumeni syndrome (LFS)

A

cancer predisposition syndrome where the molecular basis is a loss of function germline mutation in the p53 gene

inheriting 1 faulty copy of p53 increases risk of cancer and lowers median age at diagnosis