7. Molecular Basis of Colon Cancer

Question 1

What is the inheritance of familial adenomatous polyposis coli

Answer 1

autosomal dominant

Question 2

What are the features of FAP

Answer 2

large number of polyps

90% have pigmented lesions

Question 3

What is the gene defect in FAP

Answer 3

Adenamatous polyposis coli (APC)
Chromosome 5 q21-22
Mostly nonsense or frameshift mutations

Question 4

How to test for gene defect in FAP

Answer 4

Protein truncation test

Direct sequencing

Question 5

What does adenomatous polyposis coli do?

Answer 5

Binds beta-catenin

Binds microtubules

Question 6

What is beta-catenin

Answer 6

APC binds to B-catenin in the cytoplasm
Binding mediated the degradation of b-catenin (keeping levels overall low)
*If not bound to APC and degraded, b-catenin accumulates and can enter the cnuclues and bind to T-cell factor
Binding to TCF triggers transcription of genes that promote cell division

Question 7

What is the inheritance pattern of hereditary nonpolyposis coli (lynch syndrome)

Answer 7

Autosomal dominant

Question 8

What are the features of hereditary nonpolyposis coli

Answer 8

High risk of colon tumours

Low number of polyps

Question 9

What is the gene defect in hereditary nonpolyposis coli

Answer 9

In DNA mismatch repair

Question 10

Compare FAP and HNPCC

Answer 10

FAP:
Large number of polyps
Low mutation rate
High risk of cancer due to high number of polyps

HNPCC:
Low number of polyps
High mutation rate
High risk of cancer despite low number of polyps

Question 11

When is cetuximab used

Answer 11

only used where wildtype KRas

Question 12

How can aspirin prevent colorectal cancer

Answer 12

Aspirin and other NSAIDs inhibit COX-2
COX-2 increased in early stages of colorectal cancer
Increased prostaglandins synthesis
Stimulates proliferation and angiogenesis
Inhibits apoptosis