1) Oncogenes and Signalling

Question 1

What are the function of proto-oncogenes?

Answer 1

Genes coding for proteins that help to regulate cell growth and differentiation

Question 2

Give examples of mutations to DNA:

Answer 2

Deletion - bp, gene, chromosome 
Insertion - bp, virus
Substitution - bp
Amplification - gene, region, chromosome 
Translocation - chromosome

Question 3

How can viruses ‘mutate’ DNA?

Answer 3

Insertion of novel DNA (viral oncogene)

Question 4

Give examples of proteins encoded by oncogenes:

Answer 4

Growth factors e.g. PDGF
Growth factor receptors e.g. EGFR
Protein kinases
Protein that control cell cycle e.g. cyclins
Proteins involved in apoptosis e.g. bcl-2
Transcription factors e.g. myc

Question 5

Give examples of viruses that can cause cancer:

Answer 5

HPV 16/18 - cervical cancer

Hep B - hepatocellular cancer

Question 6

Give examples of chromosomal translocations in cancers:

Answer 6

c-abl (9) truncated onto bcr (22) in chronic myeloid leukaemia
c-myc (8) onto igh (14) in Burkitt’s lymphoma

Question 7

Explain how chromosomal amplification can predispose to cancer:

Answer 7

Tumour genomic instability leads to amplification and may lead to over production of normal protein e.g. growth promoter

Question 8

Describe the ras signalling pathway:

Answer 8

ras is activated by tyrosine kinase receptors and active when GTP binds. Activates the MAP kinase pathway leading to transcriptional regulation

Question 9

Where are the most common ras activating mutations found?

Answer 9

Codons 12, 13 and 61

Question 10

Why is it important to know the exact ras mutation?

Answer 10

Type of ras mutation determines prognosis in colorectal cancer (12 and 13)
Also KRAS can be used a prognostic marker

Question 11

Why is it difficult to block ras?

Answer 11

Hard to combat as it’s a single base mutation and location of changed amino acid is in pocket for GTP binding
Also, ras has widespread functions in the body

Question 12

What is a common mutation found in metastatic melanoma?

Answer 12

BRAF (50%)

Question 13

What is the mechanism of action of Vemurafenib? (why isn’t is used very often?)

Answer 13

BRAF inhibitor

Short term improvement then resistance and relapse

Question 14

What cancer is HER-2 overexpressed in?

Answer 14

Breast cancer

Question 15

How can HER-2 expression be measured?

Answer 15

Brown membrane stain for HER-2 receptors

Question 16

What is herceptin (trastuzumab)?

Answer 16

Monoclonal antibody against HER-2

Question 17

Give examples of targeted therapy for HER-2 positive breast cancer:

Answer 17

Pertuzumab - monoclonal antibody
Ado-trastuzumab emtansine - monoclonal antibody attached to chemo (advanced)
Lapatinib - kinase inhibitor (when herceptin has failed)

Question 18

What is the result of the 9;22 translocation in chronic myeloid leukaemia?

Answer 18

Fusion protein with abnormal tyrosine kinase activity

Targeted by monoclonal antibodies

Question 19

What is the result of the 8;14 translocation in Burkitt’s lymphoma?

Answer 19

Strong promoter leading to constitutive myc expression in B cells