quiz 6 dr.horwitz review slides

Question 1

Lynch syndrome is autosomal ___________(dom/recessive). It is a ______ (gain/loss) of function disease.

Answer 1

Lynch syndrome is autosomal dominant. It is a loss of function disease.

Question 2

Lynch syndrome It is a genetically heterogeneous deficiency in what type of DNA repair? What type of cancers are associated with it?

Answer 2

Genetically heterogeneous (MSH2, MLH1, MSH6, PMS2) deficiency in DNA mismatch repair. It is associated with colorectal cancer, endometrial cancer, ovarian cancer, biliary, renal collecting system, brain, but no or not much breast cancer risk.

Question 3

The hallmark of Lynch syndrome is ____________ ___________. This is caused by the failure to correct replication slippage at __________ __________ that results in changes in repeat numbers in tumor cells.

Answer 3

The hallmark of Lynch syndrome is MICROSATELLITE INSTABILITY. This is caused by the failure to correct replication slippage at REPEATED SEQUENCES that results in changes in repeat numbers in tumor cells.

Question 4

With Lynch syndrome, loss of expression of causative gene can be seen using what staining?

Answer 4

IHC can be used to see the loss of expression of MSH2, MLH1, MSH6, and PMS2 (MMR or mismatch repair genes).

In picture, PMS2 gene product has dark brown stain, tumor is in the left lower picture because it does not have it.

Question 5

What tumor suppressor gene syndrome has an APC mutation that normally blocks the Wnt/beta-catenin signaling that controls many cell grwoth pathways including cell-cell interactions and contact growth inhibition?

What organ does this mostly affect?

Where else is it found?

Answer 5

Familial adenomatous polyposis is an autosomal dominant tumor suppressor gene syndrome.

It mostly affects the colon where polyps begin in later childhood making a colectomy inevitable because cancer would be inevitable.

Extra-colonic manifestations include jaw cysts and bony and soft tissue tumors known as Gardner syndrome.