25th Jan

Question 1

Is cancer an environmental or genetic disease?

Answer 1

Cancer is a genetic disease

Although mutations in the DNA are primarily caused by environmental mutagens, it is the genetic changes that are responsible for inducing the hallmarks of cancer.

Question 2

How large is a tumour before it is usually detected?

Answer 2

> 10^9 cells

Question 3

Are tumours monoclonal?

Answer 3

Yes

Question 4

What is the evidence to show that tumours are monoclonal?

Answer 4

X-inactivation mosaics

• G6PD exists in two allelic forms on the X-chromosome
• Each cell in women will have a different X-chromosome suppressed randomly
• In leiomyomas from heterozygous women all cells within a tumour had the same allelic form of G6PD, showing they derived from the same cell.

Evidence from myelomas

• different cells have different Ab
• all cells within the same tumour have the same Ab

Evidence from chromosomal rearrangements

• Normal tissue has little chromosomal rearrangement
• Tumours all have the same chromosomal rearrangement
• In many patients with CML cancer cells can be distinguished by presence of the philadelphia chromosome which arises from a translocation between chromosomes 9q and 22q
• —exact site of breakage is identical in all leukaemic cells from a given patient

Question 5

What is Knudson’s multihit hypothesis?

Answer 5

That several different independent mutations in the lineage of a cell are required for cancer development-
i.e. can’t be developed by a single mutation.

Question 6

What are the 3 main phases of tumourigenesis?

Answer 6

The Breakthrough Phase
The Expansion Phase
The Invasive Phase

Question 7

Describe the breakthrough phase

Answer 7

A single cell develops a specific driver gene mutation and begins to divide abnormally

Question 8

Describe the Expansion Phase

Answer 8

A cell develops an additional driver gene mutation that gives rise to a benign tumour

Question 9

Describe the invasive phase

Answer 9

A cell develops an additional driver gene mutation in at least one of the indicated pathways enabling it to invade surrounding tissues

Question 10

If tumours are mainly monoclonal why are they heterogenous?

Answer 10

Tumour progression involves successive rounds of mutation and natural selection

Question 11

What elements of the tumour microenvironment can affect tumour growth?

Answer 11

Fibroblasts, myofibroblasts and carcinoma associated fibroblasts
Cells of innate immune system 
Endothelial cells, pericytes
Cells of the adaptive immune system
Extracellular matrix