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CAN > L12: Tumour Supressor Genes In Cancer > Flashcards

L12: Tumour Supressor Genes In Cancer Flashcards

1
Q

What are tumour suppressor genes role

A

To suppress cell division and suppress tumour growth

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2
Q

What mutations are head and neck cancer mostly driven by

A

P53 mutations

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3
Q

Name an example of a type of head and neck cancer

A

Oropharngeal squamous cell carcinoma (OPSCC)

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4
Q

What is OPSCC mostly driven by

A

HPV

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5
Q

What other cancer is HPV associated with

A

Cervical cancer

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6
Q

What type of HPV drives OPSCC

A

Type 16 and 18

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7
Q

How does HPV drive cancer

A

1) HPV introduces the oncogenes of E6 and E7
2) E7 inhibits RB so E2F transcription factor can cause gene transcription to go to s phase
3) E6 inhibits P53 so apoptosis cannot occur

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8
Q

Does OPSCC have mutated p53

A

No but P53 is inhibited by E6

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9
Q

Does HPV patients have metastases

A

Yes

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10
Q

What is thyroid cancer driven by

A

Uncontrolled MAPK pathway

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11
Q

What leads to the uncontrolled acivation of the MAPK pathway in terms of oncogenes

A

Mutation of RAS and BRAF

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12
Q

In papillary thyroid cancer what gene is likely to be mutated

A

BRAF

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13
Q

What does germ line mutation of PTEN lead to

A

Cowdens syndrome

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14
Q

What is cowdens syndrome

A

Autosomal dominant that leads to multi system disorders including git, thyroid, breast, skin, cranial.

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15
Q

In Colon cancer what can you get

A
  • chromosomal instability that leads to wild type of TSG
    Or
    Inactivation of DNA mismatch repairs that lead to micro-satellite instability
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16
Q

How does inactivation of DNA mismatch repair gene lead to Colon cancer

A

1) TSG becomes mutated which is usually picked up by mismatch repair genes and repaired
2) when mismatch repair genes are not functioning the TSG remains mutated leading to cancer

17
Q

What is melonoma

A

An aggressive skin cancer

18
Q

What are the common mutations that lead to melonoma

A

BRAF
CDKN2A
PTEN

19
Q

What is the most common pathway that is alters in melonoma

A

NF1/RAS pathway

20
Q

What are the tumour suppressor genes in the NF1/RAS pathways

A

NF1 and PTEN

21
Q

What are the oncogenes

A

N-ras

BRAF

22
Q

What drug is used to inhibit BRAF

A

Vemfurafenib

23
Q

What can happen to NF1

A

Become resistance due to mutation

24
Q

How can we overcome NF1 resistance

A

MEK inhibitor such as trametinib

25
Q

What other pathways are altered in skin melonoma skin

A

RB1/ CDKN2A

MDM2/TP53

26
Q

What does CDKN2A encode for

A

P14

P16

27
Q

What does P14 usually initiate

A

TP53

28
Q

What does P16 usually initiate

A

RB1

29
Q

What does loss of CDK2NA result in

A

Loss of p16 and p14 so loss of supression of TP53 and RB1

30
Q

What are TP53 and RB1

A

Tumour supressor genes

31
Q

What does supression of TP53 and RB1 result in

A

Increased cell cycle and decreased apoptosis

32
Q

What are the 2 types of colorectal cancer that you can get

A

Familial adenomatous polyposis

Hereditary non polyposis colorectal cancer

33
Q

What does familial adenomatous polyposis occur as a result of

A

Germ line mutation of APC

34
Q

How does mutation of APC lead to cancer i.e proliferation

A

1) when e-cadherin is lost in cancer beta catenin becomes free in the cell
2) free beta catenin in usually degraded by APC complex
3) when the APC is mutated this leads to accumulation of beta catenin
4) beta catenin gets inside to the cells to drive expression of genes such as Myc that leads to uncontrolled proliferation and cancer

35
Q

What does hereditary non polyposis colorectal cancer occur as a result of

A

Germ line mutation of the mismatch rapid genes that leads to microsatellite instability

36
Q

What is APC

A

A tumour suppressor gene

CAN (25 decks)

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