1. CANCER

2. Introduction What is cancer? Genetic disease of somatic cells
Rarely inherited
Unrestrained growth of cells
Abnormal proliferation
Loss of normal restraints preventing cells from spreading to other parts of the body (metastasis)

3. Cancer Clonal origin Multiple mutations are required
All cancerous cells within an individual are daughter cells from a single cancerous cell
Primary vs secondary tumors
Multiple mutations are required
Several layers of protection against development of cancer

4. Genomic Instability
Once a cancerous mutation occurs, other mutations occur more easily: mutator phenotype
Chromosomal mutations (translocations, e.g.)
Defective DNA repair
Epigenetic modifications

5. Abnormal Cell Proliferation: Cell Cycle Dysregulation
Cell cycle checkpoints keep mutated cells from dividing

6. Proto-oncogenes and Tumor-suppressor genes

7. Proto-oncogenes ras family genes Normal function Mutant
Cell cycle progress
Mutant
Oncogenes promote abnormal cell proliferation

8. Tumor Suppressor Genes
p53 family genes
Normal function
Cell cycle checkpoint regulation
G1/S and G2/M
Mutant
Allow cells with mutations to proliferate
Can lead to a mutator phenotype

9. Multi-Step Progression to Cancer
Familial adenomatous polyposis
Inherit a mutant copy of APC gene
Second mutation in the other allele  “Loss of heterozygosity”
APC is a tumor-suppressor gene
Mutation of APC  polyp formation
Further mutations result in malignant metastatic colorectal cancer

10. Multi-Step Progression to Cancer

11. Virally-Caused Cancer
2nd leading cause of human cancer is viral infection
1st cause is smoking
Typically caused by DNA viruses
Viruses rely on host cell machinery to replicate
Viruses contain genes to “turn on” host cells
Examples
HPV Human papillomavirus
HTLV Human T-cell leukemia virus
Hep B Human herpesvirus B
Epstein- Barr virus