Flashcards in Cancer: Small Bowel & Colon Deck (34):
What malignant GI tumors are derived from epithelial cells?
(2) neuroendocrine tumor
What are the common benign GI tumors?
J: This refers to clonal, polypoid mass of dysplastic epithelium with no invasion.
What is an adenoma?
In the colon, when is an adenoma considered cancer?
When it invades the submucosa.
In the small bowel, when is an adenoma considered cancer?
When it invades the lamina propia.
What gene is reliably mutated in adenomas?
What percentage of cases of colorectal cancer are due to genetic predisposition?
What are the genetic variants of colon cancer and the genes associated to them?
(1) hereditary nonpolyposis colon cancer (DNA mismatch repair)
(2) familial adenomatous polyposis colon cancer (APC)
(3) juvenile (Smad4, Alk3)
(4) Peutz-Jeghers (LKB1)
What happens to the GI epithelium in the absence of Wnt signaling?
(1) Beta-catenin is phosphorylated by the complex of APC, AXIN and GSK-3b.
(2) The phosphorylated beta-catenin is degraded.
(3) No cell proliferation.
What happens to the GI epithelium in the presence of Wnt signaling?
(1) Wnt binds to the Frizzled receptor.
(2) Phosphorylation of beta-catenin is inhibited.
(3) The monomeric beta-catenin accumulates in the cytoplasm and acts as a transcription factor (in conjunction with Tcf) for genes involved in cell proliferation.
Where in the epithelial architecture is Wnt most prevalent?
In the base of the crypts.
What happens if APC is knocked out?
Since beta-catenin cannot be phosphorylated, the cell is in a constitutively proliferative state.
What is the first step done when an adenoma is discovered?
Surgically remove it.
What is CIN?
Chromosomal instability. Gains or losses of whole or parts of chromosomes, frequently occurring with cell division resulting in karyotypic cell-to-cell variability.
What is CIMP?
CpG island methylator phenotype. Uncontrolled methylation of CpGs in promoter regions, leading to gene inactivation.
What is MSI?
Microsatellite instability. Insertions or deletions in areas of di- and trinucleotide repeats. This can lead to slippage during DNA replication.
What are sources of DNA replication stress?
(1) decreased dNTP pool
(2) DNA damage, blocking replication
(3) inaccessibility due to tertiary structure
Can lead to fork collapse, breaks, recombination, CIN.
What are the 4 major genes associated with DNA mismatch repair?
MSH2, MSH6, MLH1, PMS2.
What results from the oxidation of guanine?
8-hydroxyguanine (8-OH-G), which is recognized as thymine by DNA replication enzymes.
In what 3 ways can problems associated with guanine oxidation be solved?
(1) removal of 8-OH-G from the nucleotide pool (MTH1)
(2) removal of 8-OH-G once incorporated into the DNA (OGG1)
(3) removal of mis-incorporated adenine (MYH)
What condition is associated with a germ line mutation in the APC gene?
Familial adenomatous polyposis.
In FAP, what segments of the GI tract are at a particularly increased risk of adenocarcinoma?
The small bowel. Dysplasia can occur in the stomach, but the risk of gastric cancer is not increased.
What are some extra-intestinal manifestations of an APC gene mutation?
(1) desmoid tumors
(3) CNS tumors
What disorder is characterized by germ line mutations to DNA mismatch repair genes?
Hereditary non-polyposis coli.
J: This refers to the presence of HNPCC and sebaceous lesions.
What is Muir-Torre syndrome?
What is Turcot's syndrome?
The presence of GI malignancies and brain tumors. Either:
(1) HNPCC and glioblastomas
(2) FAP and medulloblastomas
What mutation is common in colon cancers due MSI caused by hypermethylation of promoters (rather than a germ line mutation)?
What is the most common small GI polyp?
Hyperplastic colon polyp.
Is a polyp an adenoma?
J: These GI polyps are not dysplastic or cystic and frequently result from the repair of inflammation.
What are inflammatory polyps?
J: This GI polyp is not dysplastic and is associated with Smad4 mutations.
What is a juvenile polyp?
Does the presence of a juvenile polyp indicate an increased cancer risk?
Not singly. Multiple polyps, juvenile polyposis, carries a 10% increased risk.
J: This GI polyp is characterized by arborizing smooth muscle.
What is a hamartomatous polyp?