3 major categories of inherited cancer genes
Tumor suppressor genes
DNA repair genes
Increases the rate of Polyposis Colon Cancer
Most mutations in this gene are a missense in DNA binding domain
This gene codes for a protein that binds CDKN1A promoter, increases p21 level to inhibit cell cycle progression.
If mutations are detected this gene will up-regulate PTEN and BAX to initiate apoptosis
These genes code for a protein that functions in repairing dsDNA breaks
3% of breast cancers and mutation increases lifetime risk from 12.5 tp 80%
BRCA1 and BRCA2
Tumor suppressor gene found on chromosome 17. It down regulates Ras.
Mutations in this will cause a presentation with cafe au lait spots
Example is Retinoblastoma
This model is described by the need for 2 mutations to lead to cancer.
Knudson 2-hit model
based on high frequency mutations that sum up to form carcinogensis such as colon cancer.
Example: First APC mutation, leads to 1/2 people forming a p53 mutation which leads to SMAD4 mutation as well
multi-hit concept of carcinogensis
Defect in APC gene.
Adenomas start as polyps, which may proceed to become cancerous.
More polyps with lower probability for malignancy, but the number of polyps increase odds of tumor
Familial Adenomatous Polyposis Coli
MSH2 and MLH1 mutations resulting in a loss of DNA mismatch repair. Very high penetrance for heterozygotes.
Few polyps, but the increased mutation rate increases the probability of tumor progression
Herediatry Non-polyposis colon cancer (HNPCC)
Genetic inheritance forms a paradox in regards to cellular function because of what model?
Multi-hit or the Knudson 2-hot model.
A mutated gene may not express in the cell after inheritance, until another mutation has been acquired.
Li-Faumeni syndrome gene
Familial Adenomatous Polyposis Coli gen
Breast Cancer and Ovarian Cancer gene
Breast Cancer in men gene
Ihibits p21, removing the check on the cell cycle
Multiple endocrine neoplasia
“guardian of the genome”
Mutated in >50% of cancers
This protein binds CDKN1A (which increases p21)