GI

Question 1

Name the genes most commonly mutated in Juvenile polyposis.

Answer 1

SMAD4

BMPR1A

Autosomal dominant inheritance in juvenile polyposis syndrome.

Question 2

What other GI lesions are found in patients with Juvenile Polyposis syndrome?

Answer 2

Adenocarcinoma, with many sites:

Gastric

Small intestinal

Colonic

Pancreatic

Question 3

What is the usual mutation found in Peutz-Jeghers?

Answer 3

STK11

Germline heterozygous loss of function of STK11 tumor suppressor gene that regulates AMP-activated protein kinases.

Question 4

List extraintestinal manifestations of FAP

Answer 4

Congenital hypertrophy of retinal pigment epithelium

Papillary thyroid carcinoma

Desmoid tumor

hepatoblastoma

osteoma of skull

epidermal inclusoin cysts

lipoma

nasopharyngeal angiofibroma

Question 5

Name an autosomal recessive polyposis syndrome.

Answer 5

MYH-associated polyposis

DNA mismatch repair, gene mutation on MYH

Question 6

What are the two genetic pathways for the development of colorectal carcinoma?

Answer 6

APC/Beta-catenin

MSI pathway - DNA mismatch repair resulting in microsatellite instability.

Question 7

What is the function of the APC protein?

Answer 7

Binds to and promotes degradation of beta-catenin (a component of WNT signaling pathway).

When mutated, beta-catenin not degraded; translocates to the nucleus, and activates transcription of genes including MYC and cyclinD1, which promote proliferation.

Question 8

What proto-oncogene is mutated in the classic adenocarcinoma sequence, after a second hit to the APC gene?

What other mutations follow in the sequence?

Answer 8

Activation of KRAS promotes growth and prevents apoptosis.

Additional mutations in TP53, SMAD2 and SMAD4 (effectors of TGF-b signaling; TGF-b normally inhibits the cell cycle)

See Robbins p. 815

Question 9

What are the signature mutations in MSI high colon cancers without DNA mismatch repair enzyme mutations?

Answer 9

CpG island methylation - MLH1 hypermethylated; BRAF oncogene mutation also common.

Absence of TP53 and BRAF mutations.

Question 10

List 7 causes of peritonitis.

Answer 10

Leakage of bile or pancreatic enzymes (sterile peritonitis)

Perforation/rupture of biliary system

Acute Hemorrhagic pancreatitis

Foreign material (ex. talc, sutures)

Endometriosis (irritation from hemorrhage)

Ruptured dermoid cyst (irritation from keratin)

Perforation (of abdominal organ)

Robbins p. 820

Question 11

What two criteria are needed to diagnose spontaneous bacterial peritonitis ?

Answer 11

neutrophils in ascites fluid

positive bacterial cultures

Robbins 820