Top 3 causes of death in adults
- Heart disease
- Cancer
- Cerebrovascular accident
Top 3 causes of death in children
- Accidents
- Cancer
- Congenital defects
Top 3 incidence of cancer
- Breast/prostate
- Lungs
- Colorectal
Top 3 deadly cancers
- Lungs
- Breast/prostate
- Colorectal
What are the 3 apoptotic pathways
- Perforin/Granzyme - via CD8 cells
- Intrinsic = p53 –> Bax activation, causing cytochrome C leakage
- Extrinsic = FASL-CD95 via CD8 cells
When Rb is phosphorylated by CDK/cyclin, does it release or attach to E2F
Hyperphosphorylation of Rb causes Rb to release E2F. E2F goes on to induce cell growth
Is Rb normally bound or separated from E2F
Rb is a tumor suppressor which is normally bound to E2F causing an arrest of cell growth to S phase.
When Rb is phosphorylated, is it activated or inactivated?
Phosphorylating Rb causes its inactivation meaning E2F is separated and able to cause cell growth
A germline mutation of p53 results in what diagnosis
Li-Fraumeni Syndrome
CML is a result of what translocation?
t(9:22) Philadelphia Chromosome
Is BCR or ABL on chromosome 9
ABL is located on chromosome 9
BRAF proto-oncogene is associated with what diseases?
Melanoma and Hairy cell leukemia
JAK 2 proto-oncogene is associated which which disease
Polycythemia vera
Myc is found on what chromosome?
Chromosome 8
It is translocated to Chromosome 14 in Burkitt lymphoma
Follicular lymphomas is a result of what translocation?
t(14:18)
14 = Ig heavy chain
18 = Bcl2
Pathogenesis of Follicular lymphoma translocation consequences
Bcl-2 is located on chromosome 18. When translocated to the heavily active Ig Heavy chain area on chromsome 14, it causes an increase of Bcl-2.
Bcl-2 is anti-apoptotic. In the follicles, many B cells are supposed to die but with an increase in Bcl-2, there is no apoptosis –> a build up of mutated B-cells
CCND1 translocation results in what kind of lymphoma?
Mantle cell lymphoma t(11:14)
Chromosome 11 = cyclin
MEN1 is a tumor suppressor or a proto-oncogene?
RET is a tumor suppressor or proto-oncogene?
MEN1 is a tumor suppressor (2 hit)
RET is a proto-oncogene (1 hit)
APC, BRCA, MEN1, p53, Rb, VHL, and WT1 are examples of proto-oncogenes or tumor suppressors?
Tumor suppressors
BCR-ABL, BRAF, JAK 2, myc, Bcl-2, HER2, CCND1, and Kras are examples of proto-oncogenes or tumor suppressors?
Proto-oncogenes
Proto-oncogenes become oncogenes via gain of function or loss of function?
Proto-oncogenes a pro-growth. A gain of function mutation (1 hit) causes uncontrolled cell growth. Example ) Kras mutation –> polyp to uncontrolled growth
What is found on chromosome 14 and poses an issue in the translocation of
t(8:14) - Burkitt
t(11:14) - mantle cell lymphoma
t(14:18) - follicular lymphoma
Chromosome 14 has the Ig Heavy chain location of B cells. When other areas are translocated here, there is a very high expression of these proteins.
Example) Mantle cell lymphoma
Chrom. 11 = Cyclin. Increased cyclins = more Rb phosphorylation = more E2F cell cycle growing
Azathioprine and 6-mercaptopurine mechanism of action
Purine analog, disrupts transcription
What drug is contraidindicated with azathioprine/6 mercaptopurine?
Allopurinol
Xanthine oxidase is needed to inactivate the 6-mercaptopurine. Allopurinol inhibits xanthine oxidase so if given together, there will be high, toxic levels of 6 mercaptopurine
