Pathology 9 - Neoplasia 3 Flashcards

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 offTurn off genes that stop cells dying = evasion of apoptosisBreak 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)

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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

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3
Q

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

A

InitiationPromotionPersistence

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4
Q

What is initiation?

A

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

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5
Q

What is promotion?

A

Further accumulation of mutationsAdditive effectIncreased growthOften results in a “pre-malignant” phase - dysplasia

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6
Q

what is progression?

A

Cell has developed mutations that allow it to grow in na autonomous fashionUnregulated abnormal growthCells have the ability to invade connective tissue and blood vesselsMalignancy has now been achieved

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7
Q

What are the 3 categories of growth factors?

A

Receptors with intrinsic tyrosine kinase activity7 transmembrane G protein-coupled receptorsReceptors without intrinsic tyrosine kinase activity

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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

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9
Q

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

A

ERGF over expression (most cancers)RAS mutation RAF mutationMyc mutation(we can use “personalised” drugs that specifically target these mutations)*these are all photo-oncogenes

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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

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11
Q

What is RAS?

A

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

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12
Q

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

A

ColonLungPancreaticBladderRenalMelanoma

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13
Q

What is BRAF?

A

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

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14
Q

What cancers are associated with (B)RAF?

A

Melanoma (50% are RAF mutated)Some colonic malignancies

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15
Q

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

A

Vemurafanib

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16
Q

What is Myc?

A

A nuclear transpiration factor that promotes growth - DNA replicationPro-oncogene

17
Q

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

A

LymphomaNeuroblastomaSmall cell carcinoma of the lungBurkitt 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-cateninOvarian cancerEndometrial cancerSarcomas

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 cycleIf 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 pathwayTherefore 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

BreastOvarianPancreatic

33
Q

What genes are involved in evasion of apoptosis and how?

A

p53 and BCL2 p53 increases levels of BAXBAX stops BCL2BCL2 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