Sesh 9- Neoplasia 3

Question 1

What % do extrinsic factors account for a population’s cancer risk?

Answer 1

85%

Question 2

What are the 3 main categories of extrinsic carcinogens?

Answer 2

1. Chemicals
2. Radiation
3. Infection

Question 3

Which test is used to show initiators are mutagens and promoters cause prolonged proliferation?

Answer 3

The Ames test.

Question 4

What is a pro-carcinogen?

Answer 4

A carcinogen requiring conversion to by liver cytochrome P450’s to become carcinogenic.

Question 5

What is a complete carcinogen? Give an example.

Answer 5

A carcinogen that is an initiator and a promoter e.g. tobacco smoke.

Question 6

By which two ways can radiation cause DNA damage?

Answer 6

1. Directly e.g base change, double strand DNA breaks

2. Indirectly by free radical production

Question 7

How can some infections be carcinogenic without directly affecting genes controlling cell growth?

Answer 7

• Can cause chronic tissue inflammation & the resulting regeneration is either:
• a promoter for pre-existing mutations
• or causes a new mutation via DNA replication errors

Question 8

Why is HPV a direct carcinogen?

Answer 8

It expresses:

• E6 proteins- directly inhibits p53
• E7 proteins- directly inhibits retinoblastoma protein

Question 9

How does HIV act as an indirect carcinogen?

Answer 9

-Indirectly lowers host immunity, making them vulnerable to other carcinogenic infections e.g. HHV8 causing Kaposi sarcoma

Question 10

How can the 2 hit hypothesis be applied to familial cancers?

Answer 10

• 1st hit= germline mutation

- 2nd hit= somatic mutation

Question 11

Does the 2 hit hypothesis apply to tumour suppressor genes or proton-oncogenes?

Answer 11

Tumour suppressor genes, as both alleles need to be inactivated (1 hit for each allele) to favour neoplastic growth.

Question 12

What is the normal role of RAS?

Answer 12

• Is a G protein that activates a signalling cascade causing DNA to transcribe the cyclin D gene
• Gene then activates CDK which phosphorylates and inactivates retinoblastoma protein, allowing the cell to enter the cell cycle

Question 13

What type of gene is the retinoblastoma (RB) gene?

Answer 13

Tumour suppressor

Question 14

What is HER2?

Answer 14

A proto-oncogene encoding a growth factor receptor

Question 15

What is xeroderma pigmentosum due to?

Answer 15

Autosomal recessively inherited mutations in DNA repair genes affecting nucleotide excision repair, leading to genomic instability.

Question 16

What type of cancer are patients with xeroderma pigmentosum very susceptible to?

Answer 16

Skin cancer

Question 17

What are the normal roles of BRCA1/2 genes?

Answer 17

Repair of double strand DNA breaks

Question 18

What is the adenoma-carcinoma sequence?

Answer 18

• The step-wise accumulation of mutations in epithelium over time, leading to dysplasia, adenoma and then carcinoma formation.
• Cancer progression
• 1st hit inherited or somatic mutation of tumour suppressor gene
• 2nd hit= inactivation of normal alleles
• Then get homozygous loss of extra tumour suppressor genes
• Finally get additional mutations to form a carcinoma

Question 19

What are the 6 hallmarks of cancer? Which one is exclusive to malignant neoplasms?

Answer 19

1. Self-sufficiency in growth signals
2. Resistance of anti-growth signals
3. Induce angiogenesis
4. Resist apoptosis
5. Cell immortalisation (activation of telomerase genes)
6. Invasion and metastases- exclusive to malignant

Question 20

Which gene is mutated in patients with familial adenomatous polyposis (FAP)?

Answer 20

• APC on chromosome 5q21

- Encodes protein that binds to microtubule bundles

Question 21

In which inherited disorder do patients develop colonic adenomas that carpet the mucosal surface, and often develop colon cancer before the age of 50 if untreated?

Answer 21

Familial adenomatous polyposis (FAP)

Question 22

What type of gene is mutated in HNPCC?

Answer 22

DNA mismatch repair gene