Flashcards in GI cancer syndromes Deck (46)
Prevalence of CRC in USA?
Risk factors for CRC
Pers. hx adenomas, pers/fam hz CRC, low-fiber/high-fat diet, aging, IBD (not IBS)
Risk for CRC if have IBD
HNPCC is __% of CRC, FAP is ___% of CRC, other rare syndromes ___%
5%, 1%, 0.1%
APC de novo mutation rate
Desmoid tumor – what is it, which condition is it associated with?
Connective tissue tumor, APC/FAP
CHERPE – can it be seen by eye or do you need ophthalmologist
Yes, need ophthalmologist
Gardner syndrome. Gene? Symptoms?
“FAP plus” APC gene variable – polyps AND 1. Epidermoid cysts, 2. Osteomas, 3. Extra teeth, 4. CHERPE, 5.desmoid tumors
If universal APC/FAP genetic screening were a thing, what might be an issue with screening unaffected people with fam hx of APC?
Genetic testing doesn’t pick up all forms of FAP, so can’t screen unaffected people if a mutation is not known in the family.
I1307K – missense/gets hypermutable region - in which gene? associated with which ethnic group? What does it do?
APC. Ashkenazi jews. Colon cancer risk =~ risk if 1 FDR with CRC… NOT classic FAP! More mild.
MYH – do they ultimately need colectomy?
Yes, but they have fewer adenomatous polyps
MYH – carrier frequency?
1% (carriers unaffected…or slightly increased risk of CRC...~7% vs 5-6%)
Bethesda guidelines – purpose?
Which tumors to test for IHC/microsatellite instability (lynch)
Endometrial ca risk in Lynch?
Microsatellite instability – what % of sporadic tumors?
When is BRAF mutation testing done?
When IHC staining is missing MLH1 and PMS2;
if mutation in BRAF, then MLH1 absence is due to somatic methylation defect. NOT lynch.
Can IHC testing be done on endometrial cancer?
When is EPCAM mutation testing done? What is EPCAM mechanism of action? Is this heritable?
If loss of MSH2+MSH6 on IHC.
3’ deletion of EPCAM gene leads to: inactivation of MSH2 through hypermethylation of its promoter.
Yes, EPCAM mutation is heritable/ causes Lynch.
Cancers associated with Lynch syndrome
endometrium, ovary, stomach, small intestine, hepatobiliary tract, urinary tract, brain, and skin
Lynch: END OV STOiSIsm, BRAhSKI. + hep and urinary tracts.
Cancers associated with Muir-Torre (variant of HNPCC)
HNPCC + sebaceous adenoma (sweat gland) + keratoacanthoma ... (type of squamous cell carcinoma)
Muir-Torre is a sexy, sweaty, latin beast.
Cancer associated with Turcot
colonic polyposis + medulloblastoma (if APC mutation) or glioblastoma (MMR gene mutation) .... Turcot sounds like a "brainy" French dude.
Cafe au lait spots are a feature of this cancer syndrome. Name that syndrome!
Constitutional Mismatch Repair/ Homozygous PMS2 Deficiency (cafe au lait spots, early CRC, leukemia, lymphoma, child brain tumors, death in 20s)
Lynch-y cancers are proximal or distal? Right or left sided?
Proximal, Right-sided. Mr. Lynch was a righteous dude.
Amsterdam Criteria. Go!
3 relatives, at least 1 FDR of other.
1 CRC under 50.
---> If meets then HNPCC.
can also be used to dx Syndrome X.
What is special about how polyps progress to cancer in Lynch syndrome?
There is accelerated progression from normal -->polyp --> lynch.
__% of sporadic tumors have Microsatellite Instability (MSI), usually due to ___
10-15% have MSI, usually due to BRAF mutations (causes methylation defect for MLH1.)
Most common Lynch genes mutated
MLH1, MSH2 ("bottom" proteins in MMR machinery)
When doing IHC, PMS2/MLH1 are both absent what percent of time?
When doing IHC, MSH2 +/- MSH6, or PMS2 are absent what percent of time?