*Pathology (5) Flashcards Preview

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Flashcards in *Pathology (5) Deck (36)
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1
Q

What are the 4 cancer causing groups of genes?

A

Oncogenes - turn these up (cause mutation from photo-oncogene to oncogene)
Tumour supressor genes - turn these off
Turn off genes that stop cells dying = evasion of apoptosis
Break the spell checker genes = allows accumulation of spelling mistakes in oncogenes, tumour suppressors and those that avoid apoptosis (permits progression through the cell cycle even with mistakes)

2
Q

How does cancer develop?

A

You need 2 mutations in a gene for cancer to develop (2 hit hypothesis)
Once you have the 2 hits the cells will begin to rapidly proliferate and will accumulate more and more mutations until they become a self sustaining growth
*the 2 it hypothesis refers to tumour suppressor genes

3
Q

What are the 3 key stages in the development of cancer?

A

Initiation
Promotion
Persistence

4
Q

What is initiation?

A

The 1st mutation is acquired (often in one of the group of 4)

5
Q

What is promotion?

A

Further accumulation of mutations
Additive effect
Increased growth
Often results in a “pre-malignant” phase - dysplasia

6
Q

what is progression?

A

Cell has developed mutations that allow it to grow in na autonomous fashion
Unregulated abnormal growth
Cells have the ability to invade connective tissue and blood vessels
Malignancy has now been achieved

7
Q

What are the 3 categories of growth factors?

A

Receptors with intrinsic tyrosine kinase activity
7 transmembrane G protein-coupled receptors
Receptors without intrinsic tyrosine kinase activity

8
Q

What is the MAPK/ERK pathway?

A

a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell

9
Q

What lesions in the ERK-signalling pathway can cause cancer? (4)

A
ERGF over expression (most cancers)
RAS mutation 
RAF mutation
Myc mutation
(we can use "personalised" drugs that specifically target these mutations)
*these are all photo-oncogenes
10
Q

What tyrosine kinase receptors are sometimes mutated in gastrointestinal stromal tumours (GIST) and leukemias?
What therapeutic agent is used to treat this?

A

C-KIT (growth receptor)

Imatinib

11
Q

What is RAS?

A

RAS is a family of related proteins that are involved in transmitting signals within cells
when switched on, RAS turns n other proteins, which ultimately turns on genes involved in cell growth, differentiation and survival
as a result, mutations in RAS can lead to the production of permissively active RAS proteins
(GTP binding proteins)
Proto-oncogene

12
Q

What type of cancers commonly have RAS mutations? (6)

A
Colon
Lung
Pancreatic
Bladder
Renal
Melanoma
13
Q

What is BRAF?

A

A downstream of receptor and RAF - it is a photo-oncogene involved in the ERK-signalling pathway
Proto-oncogene

14
Q

What cancers are associated with (B)RAF?

A

Melanoma (50% are RAF mutated)

Some colonic malignancies

15
Q

What is an inhibitor of BRAF that is licensed for melanoma treatment?

A

Vemurafanib

16
Q

What is Myc?

A

A nuclear transpiration factor that promotes growth - DNA replication
Pro-oncogene

17
Q

What cancers are commonly affected by Myc mutation? (3)

A

Lymphoma
Neuroblastoma
Small cell carcinoma of the lung
Burkitt lymphoma

18
Q

What is the most common mutated kinase receptor in cancer?

A

P13K

19
Q

What pathway is APC a part of?

A

Canonical Wnt Pathway

20
Q

Apart from APC, what other protein in the canonical WnT pathway can become mutated causing cancer?
What cancers is this commonly mutated in?

A

Beta-catenin
Ovarian cancer
Endometrial cancer
Sarcomas

21
Q

What does a mutation in JAK2 commonly occur in?

A

Haematological malignancies

22
Q

What type of proteins are often prefixed with “p”?

A

Tumour supressor genes

23
Q

What is the most commonly mutated protein across all cancers?

A

p53 - tumour supressor gene

24
Q

What does p53 do?

A

Senses DNA abnormalities at G1 and pauses the cell cycle - increases levels of p21 which is a CDK inhibitor
If DNA is repaired, p53 restarts the cell cycle
If repair is not possible, p53 initiates apoptosis

25
Q

What is CDK activated by?

A

Cyclins

26
Q

What cycle does p53 initiate apoptosis by?

A

BAX cycle

27
Q

What Von-Hippel Lindau disease?

A

a disease which results from a mutation in the von Hippel–Lindau tumor suppressor gene which causes multiple tumours to develop (mostly renal cancers)- loss of a functioning VHL gene increases levels of angiogenic growth factors

28
Q

What does PTEN do?

A

Increased transcription of p27 - p27 blocks CDKs and cell cycle progression and therefore inhibits P13K/AKT pathway
Therefore a mutation in this causes proliferation in an uncontrolled manner

29
Q

What are 4 examples of DNA repair genes?

A

MLH1, MLH2, PMS1, PMS2 - mutations in these can lead to the likes of HNPCC and Muir Torres

30
Q

What parts of DNA do DNA repair genes specifically look at?

A

Microsatellite regions

31
Q

What type of genes is BRCA?

A

DNA repair genes/ tumour supressors

32
Q

What types of cancers do BRCA mutations increase your risk of?

A

Breast
Ovarian
Pancreatic

33
Q

What genes are involved in evasion of apoptosis and how?

A

p53 and BCL2
p53 increases levels of BAX
BAX stops BCL2
BCL2 is anti-apoptotic

34
Q

Is Bcl2 pro or anti-apoptotic?

A

Anti-apoptotic

35
Q

Is Bcl2 normally on or off in normal lymph node follicles?

A

Off - need apoptosis to get rid of self reactive lymphocytes

36
Q

How do many lymphoma cells avoid apoptosis?

A

By switching on BCL2