L12: Tumour Supressor Genes In Cancer

Question 1

What are tumour suppressor genes role

Answer 1

To suppress cell division and suppress tumour growth

Question 2

What mutations are head and neck cancer mostly driven by

Answer 2

P53 mutations

Question 3

Name an example of a type of head and neck cancer

Answer 3

Oropharngeal squamous cell carcinoma (OPSCC)

Question 4

What is OPSCC mostly driven by

Answer 4

HPV

Question 5

What other cancer is HPV associated with

Answer 5

Cervical cancer

Question 6

What type of HPV drives OPSCC

Answer 6

Type 16 and 18

Question 7

How does HPV drive cancer

Answer 7

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

Question 8

Does OPSCC have mutated p53

Answer 8

No but P53 is inhibited by E6

Question 9

Does HPV patients have metastases

Answer 9

Yes

Question 10

What is thyroid cancer driven by

Answer 10

Uncontrolled MAPK pathway

Question 11

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

Answer 11

Mutation of RAS and BRAF

Question 12

In papillary thyroid cancer what gene is likely to be mutated

Answer 12

BRAF

Question 13

What does germ line mutation of PTEN lead to

Answer 13

Cowdens syndrome

Question 14

What is cowdens syndrome

Answer 14

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

Question 15

In Colon cancer what can you get

Answer 15

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

Question 16

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

Answer 16

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

Question 17

What is melonoma

Answer 17

An aggressive skin cancer

Question 18

What are the common mutations that lead to melonoma

Answer 18

BRAF
CDKN2A
PTEN

Question 19

What is the most common pathway that is alters in melonoma

Answer 19

NF1/RAS pathway

Question 20

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

Answer 20

NF1 and PTEN

Question 21

What are the oncogenes

Answer 21

N-ras

BRAF

Question 22

What drug is used to inhibit BRAF

Answer 22

Vemfurafenib

Question 23

What can happen to NF1

Answer 23

Become resistance due to mutation

Question 24

How can we overcome NF1 resistance

Answer 24

MEK inhibitor such as trametinib

Question 25

What other pathways are altered in skin melonoma skin

Answer 25

RB1/ CDKN2A | MDM2/TP53

Question 26

What does CDKN2A encode for

Answer 26

P14 | P16

Question 27

What does P14 usually initiate

Answer 27

TP53

Question 28

What does P16 usually initiate

Answer 28

RB1

Question 29

What does loss of CDK2NA result in

Answer 29

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

Question 30

What are TP53 and RB1

Answer 30

Tumour supressor genes

Question 31

What does supression of TP53 and RB1 result in

Answer 31

Increased cell cycle and decreased apoptosis

Question 32

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

Answer 32

Familial adenomatous polyposis | Hereditary non polyposis colorectal cancer

Question 33

What does familial adenomatous polyposis occur as a result of

Answer 33

Germ line mutation of APC

Question 34

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

Answer 34

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

Question 35

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

Answer 35

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

Question 36

What is APC

Answer 36

A tumour suppressor gene