Tumors of the Small and Large Bowel Flashcards
(33 cards)
Are adenocarcinomas and neuroendocrine tumors (NETs) derived from different cells of origin?
Apparently not, they just have different mutations that drive different tumor phenotypes.
Where are most NETs?
in the GI tract.
When should people without other risk factors start getting colonoscopies?
At age 50.
6 risk factors for GI cancers? Which one is most important?
Age - most important Diet Environment Obesity Genetic IBD
Does chronic mucosal injury, eg. from UC, increase cancer risk?
Yup.
What happens if you knock out both copies of APC?
Adenoma. Loss of APC is sufficient for adenoma. She emphasized this a lot.
About how long, on average, does it take to go from adenoma to adenocarcinoma?
About 10 years.
Where must colon tumors get before they can metastasize? How does this contrast from other parts of the GI tract?
The submucosa.
In other parts of the GI tract, tumors can metastasize via lymphatics in the basal lamina.
4 autosomal dominant genetic conditions that predispose to colon cancer? What’s affected in each?
Hereditary Nonpolyposis Colon Cancer (HNPCC) - mismatch repair.
Familial Adenomatous Polyposis (FAP) - APC.
Juvenile. SMAD-4.
Peutz-Jeghers. STK-11/LKB-1
Most common site for adenomas in the colon?
The cecum.
What effect do each APC and Wnt have on beta-catenin?
APC promotes beta-catenin degradation.
Wnt promotoes beta-catenin survival -> acting as transcription factor.
What does beta-catenin do?
Promotes cell proliferation.
Where in the crypt should there and shouldn’t there be Wnt/ beta-catenin activity?
There should be activity at the base of the crypt (stem cells, etc.).
There should not be activity at the surface epithelium.
How does beta-catenin affect adhesion?
It seems to be important in cadherin function.
2 major molecular classifications of colon cancer?
Chromosomal instability neoplasms (CIN) - the chromosomes break and rearrange.
Microsatellite instablity - germ line or sporadic.
What’s CIMP?
CpG island methylator phenotype: uncontrolled methylation -> gene inactivation.
What is microsatellite instability (MSI)?
Insertion or deletions in areas of di- or trinucleotide repeats.
What process is thought to lead to chromosomal instability (CIN)?
Fork collapse…. replication fork gets messed up, free ends of DNA stick onto things.
3 things that can contribute to fork colllapse / chromosomal instability?
Decreased dNTP pool.
DNA damage that blocks replication.
Alterations in tertiary structure.
Name 2 pairs of genes that work to do DNA mismatch repair?
MSH2 and MSH6.
MLH1 and PMS2.
What protein removes hyrdroxylated guanine (8-OH-G) from the nucleotide pool?
MTH1
What protein removes 8-OH-G after it’s been incorporated into DNA?
OGG1
What protein removes mis-incorporated A (caused by 8-OH-G)?
MYH
responsible for an autosomal recessive colon cancer syndrome
In what gene do people already have 1 hit when they have FAP? Result?
APC.
Recall 2 hits in APC -> adenoma.
People with FAP have tons of adenomas, thus more chances of progression to cancer.
