Genetic Model for Colorectal Tumorigenesis

Question 1

What do most malignant colorectal carciomas arise from?

Answer 1

Pre-existing benign tumours (adenomas)

Question 2

What 2 things both contribute to the development of CRC?

Answer 2

• Genetic factors

- Environmental factors

Question 3

Which, of activation of oncogenes, and inactivation of TSGs, occur in CRC?

Answer 3

Both

Question 4

Which, of activation of oncogenes, and inactivation of TSGs, are dominant in CRC?

Answer 4

TSG inactivation

Question 5

How many mutations are required in different genes for a malignant tumour to develop?

Answer 5

4 or 5

Question 6

What is responsible for determining the tumours biological properties?

Answer 6

The total accumulations of mutations, rather than the order they were acquired

Question 7

In CRC, do all mutant TSGs have to be mutated homozygously to exert their effects?

Answer 7

No, some can work when heterozygous. This is true for some other common epithelial neoplasms.

Question 8

Are all CRCs monoclonal or polyclonal?

Answer 8

Monoclonal

Question 9

What does this monoclonal population in CRC indicate?

Answer 9

One or a small number of cells initiate neoplasia via clonal expansion

Question 10

What type of mutation (gene specific) is found in roughly 50% of all CRCs, and about 50% of adenomas larger than 1cm?

Answer 10

Ras gene mutation

Question 11

What does this susggest about the progression of tumours with ras mutations compared to without?

Answer 11

A ras mutations means the adenoma is more likely to progress to carcinoma than if it lacks a ras mutation