DNA Mismatch Repair Continued

Question 1

What is the phenotype of HNPCC called ?

Answer 1

Micro satellite Instability (MSI)

Question 2

What is micro satellite instability (MSI)?

Answer 2

A signature “symptom” of cancer with mismatch repair defect. Repeated sequences over and over and over e.g.: CACACACACACA

Question 3

What kind of mutation does micro satellite instability have?

Answer 3

A recessive mutation

Question 4

What is the difference in number of mutations between mismatch repair deficient cancer cells and a typical cancer cell?

Answer 4

MMR deficient cancer cells have about 1700 mutations compared to about 70 in a typical cancer cell

Question 5

What is the problem with MSI (microsatellite Instability)?

Answer 5

DNA Pol has a hard time copying the same thing over and over and over and can make a mistake.

Question 6

What happens in MSI if you don’t have a good mismatch repair system?

Answer 6

You land up having lots of copies of “CACACA” in the next generation e.g.: 7 instead of 6 copies

Question 7

Is HNPCC a death sentence?

Answer 7

NO, there is a screening program for HNPCC patients - annual screening 25 onwards or beginning no later than 5 years before the lowest age of onset in family.

Question 8

Keytruda is a new drug approved in May that may help who?

Answer 8

Patients with METASTATIC colorectal cancer who have a mismatch repair deficiency or MSI - high tumors who are less likely to respond to conventional chemotherapy.

Question 9

What is the percentage of colon cancers that are MMR deficient?

Answer 9

12-15% of colon cancers have this deficiency

Question 10

What is the function of each of the dimer components of Mut L alpha ?

Answer 10

Mut L alpha (MLH1 and PMS2)

MLH1 - triggers cleavage of the new strand

PMS2 - nicks DNA on other side of mismatch

Question 11

What does it mean that 12-15% of colon cancers are MMR deficient?

Answer 11

1. They can be hereditary

2. Methylation-based silencing of (mostly) MLH1 gene