Molecular Basis of Carcinogenesis II Flashcards
What is Familial Adenomatous Polyposis (FAP)?
- leads to extensive polyp formation in the GI tract
- 90% will develop carcinoma by age 50
- due to alterations in APC inherited autosomal dominant pattern
What chromosome is APC gene on?
chromosome 5
What does the APC gene encode?
a cytoplasmic protein that scavenges for cytoplasmic and unbound beta catenin and induces degradation
Where is beta-catenin located in normal cells?
the plasma membrane. It is bound to E-cadherin
What happens if APC does not degrade cytoplasmic beta-catenin?
beta-catenin goes to the nucleus to up regulate the oncogene c-myc. This induces a myriad of pro-oncogenic signaling and proliferation
What carcinogenesis syndromes is BRCA1 associated with?
breast and ovary
Genetically, inherited cases of breast cancer show what?
LOH for the BRCA1 gene with mutation of the second BRAC1 gene
How often do spontaneous breast cancers demonstrate BRCA1 mutations?
rarely
At what location are mutational events in BRCA1 at higher risk for breast and ovarian cancer?
5’ end
What is the immunophenotype of BRCA1?
- high nuclear grade
- high frequency of p53 mutations
- negativity for expression of the estrogen and progesterone receptor
What mutation can result in men developing breast cancer?
BRCA2
What is the immunophenotype of BRCA2?
- p53 mutation
- ER/PR positivity
- worse prognosis
What is the “genotype-phontype correlation” of BRCA2?
- exon 11 mutation - breast and ovarian cancer
- N- or C- termini - only breast
In what percentage have p53 mutations been identified?
50%
Why was p53 originally thought to be an oncogene?
Because some p53 gene mutations are dominant to wt p53
- p53 mutations encode an abnormal protein that binds to and inactivates p53
