Colon Cancer

Question 0

What kind of lesion can precede an easily visible polyp?

Answer 0

An aberrant crypt focus.

Question 1

What are 2 stem cell types in intestinal crypts? How does their proliferative activity vary?

Answer 1

4+ stem cells: normally quiescent.
Columnar Basal Cells (CBCs): highly proliferative.
(not sure why this matters…)

Question 2

What triggers adenomatous proliferation 80% of the time?

Answer 2

Loss of APC!

Question 3

What are 3 oncogenes that commonly are overexpressed / hyperactive in colorectal cancer? (the 1st one is probably most important)

Answer 3

K-ras
myc
src

Question 4

4 tumor suppressor genes often lost in CRC?

Answer 4

APC
DCC
SMAD4
p53 <- loss of p53 seems to precipitate switch from adenoma to carcinoma.

Question 5

What effect do APC loss of function mutations have?

Answer 5

APC is no longer able to suppress beta-catenin activity -> leading to cell proliferation.

Question 6

Review: What signaling pathway normally activates beta-catenin?

Answer 6

Wnt signaling

Question 7

Review: What’s a germline mutation in APC called?

Answer 7

FAP

Question 8

What’s a known hereditary cause of CRC that’s not FAP?

Answer 8

Lynch syndrome aka. HNPCC

Question 9

What genes can be lost in Lynch syndrome? What sort of “genetic lesion” causes this?

Answer 9

Microsatellite instability (MSI) causes loss at least one of…
MSH2 and MSH6
MLH1 and PMS2

Question 10

What prostaglandin-related gene is upregulated in many colon cancers?

Answer 10

COX-2

Question 11

What percentage of people with FAP will develop colon cancer?

Answer 11

100%
(thus treatment is often eventually total colectomy)
(but then can get cancers elsewhere later)

Question 12

Duodenal, desmoid, osteoma, brain, skin, and other cancers are associated with which hereditary CRC syndrome?

Answer 12

FAP (specifically, Gardner’s syndrome)

Question 13

How are APC genes usually knocked out? Do variations matter?

Answer 13

Usually by stop codons.

Phenotype of disease can vary with the way in which the gene is altered.

Question 14

What percent of FAP cases are de novo mutations?

Answer 14

30%

Question 15

Which is more common: Lynch syndrome or FAP?

Answer 15

Lynch syndrome is more common - but not as many people with it develop CRC (it’s still really high, but less than 100%)

Question 16

Where in the colon are polyps associated with Lynch syndrome most common?

Answer 16

On the right, ascending colon.

Question 17

Cancers of the endometrium, ovary, stomach, urinary tract, small bowel, pancreas, bile duct, and skin sebaceous glands… are associated with which hereditary CRC syndrome?

Answer 17

Lynch syndrome - and they’re common here.

43% of women with Lynch syndrome will have had endometrial cancer by age 75ish

Question 18

Is screening for fecal occult blood effective at preventing CRC?

Answer 18

Yes. It’s not as good as colonoscopy, but it works.