1. Cancer

2. Cancer is a disease of the cell cycle Caused by one or more of the following: Increase in growth signals Loss of inhibitory signals In addition, tumors must: Express telomerase Stimulate angiogenesis

3. Proto-oncogenes & Oncogenes Proto-oncogenes may have many functions: Promoting cell division Promoting programmed cell death Gain-of-function mutations in promotors, or Loss-of-function mutations in inhibitors may convert proto-oncogenes into oncogenes

4. Generally only one copy of an oncogene (i.e. one mutation) is necessary to trigger the development of a tumor.

5. ras: Example of a Proto-oncogene The ras gene codes for a protein involved in transduction of growth stimuli Mutation may cause ras to be “turned on” all the time

6. Tumor Suppressor Genes Tumor suppressor genes make proteins that: Stop the cell cycle in cells with DNA damage Repair damaged DNA Trigger programmed cell death (apoptosis) in cells with DNA damage

7. Generally, both copies of a tumor suppressor gene must be mutated. Germ-line mutations have resulted in mutant tumor suppressor variations being incorporated into the genome Since tumor suppressor genes protect from mutations, the loss of them allows other DNA mutations (for example, mutations of proto- oncogenes to oncogenes) to accumulate.

8. BRCA I, BRCA II, & TP53: Tumor Suppressor Genes Mutant BRCA I & BRCA II increase chance of breast cancer Mutant TP53 increases chance of a variety of cancers