Sporadic colorectal cancer

Question 1

How does sporadic colorectal cancer arise?

Answer 1

Accumulation of acquired “driver” mutations

Question 2

Explain adenom-carcinoma sequence

Answer 2

Normal (APC mutation) early stage adenoma (KRAS mutation) larger adenoma (18q mutation SMAD2/4) larger adenoma (TP53 mutation) high grade, late stage adenoma

Question 3

In adenoma-carcinoma sequence why do mutations appear in a certain order?

Answer 3

Each mutation must have a selective advantage at that stage

Question 4

Testing performed for sporadic colorectal cancer

Answer 4

Sequencing of mutational hotspots in KRAS, NRAS, BRAF, PIK3CA (sanger or pyro)

Question 5

Treatment offered to individuals who are WT for all four genes tested

Answer 5

Anti-EGFR monoclonal antibody treatment (cetuximab)

Question 6

What is the EGFR pathway?

Answer 6

It is a signalling pathway that promotes cell division when a mutation is present

Question 7

Can you target EGFR if KRAS has a mutation?

Answer 7

No, can only target EGFR if downstream genes WT

Question 8

Explain Dukes colorectak cancer staging

Answer 8

A- invasion into but not through bowel wall
B-Invasion through bowel wall but not involving lymph nodes
C - involvement of lymph nodes
D - widespread metastases