Cancer 1 + 2 Flashcards
Two types of genes are involved in genetic causes of cancer. What are they?
Oncogenes and tumor suppressor genes.
Overactivity of ___, from a single mutation (dominant) event causes cell proliferation and gain of function.
Underactivity of ___, caused by two mutations (recessive) leads to loss of function and potentially cancer.
oncogenes.
tumor suppressor genes.
A third group of genes play a role in cancer as well. These genes, ___, are a subset of tumor suppressor genes.
DNA maintenance genes, which include DNA repair genes, checkpoint genes, etc.
The first human oncogene discovered was ___, and it is a monomeric ___ for signal transduction.
Ras.
GTPase.
Activation of ___ (normal genes required for cell division/growth), when hyperactivated or over-expressed, can become oncogenes to drive cell proliferation.
proto-oncogenes.
What are the 4 mechanisms of oncogene activation?
- Deletion or point mutation: makes hyperactive protein in normal amounts (Ex: Ras 12 Gly to Val: keeps Ras protein in active state)
- Regulatory mutation: produces more protein.
- Gene amplification: multiple gene copies = protein overproduced.
- Chromosomal rearrangement: protein overproduced.
The Bcl2 locus on chromosome 18 undergoes a reciprocal translocation with part of chromosome 14. Bcl2 is now under control of Ab Heavy chain gene, very active in B cells. This prevents apoptosis of damaged cells because instead of making ___, the cell makes a lot of Bcl2.
antibodies.
What are the two major categories of tumor suppressor genes, and list a few examples.
- proteins that normally restrict cell growth and proliferation. (Cell cycle inhibition proteins like Rb, CKI, proteins that promote apoptosis like caspases)
- proteins that maintain integrity of the genome. (Checkpoint control proteins like ATM, ATR).
40% of retinoblastoma is familial. How many eyes are affected?
60% of retinoblastoma is sporadic. How many eyes are affected?
Is retinoblastoma dominant or recessive?
familial = both eyes.
sporadic = one eye.
recessive.
For familial (hereditary) Rb, ___ occurs from a somatic event that eliminates the one good copy of the gene, allowing the tumor to form.
For ___ Rb, you start with 2 normal genes and need a two-hit mutation to cause a tumor.
loss of heterozygosity (LOH).
sporadic.
Rb normally inhibits E2F and cell division. ___ of Rb inactivates Rb and does not allow it to bind to E2F.
Phosphorylation.
For colorectal cancer, a colonoscopy can detect small, protruding benign tumors called polyps, aka an ___. The polyp is a precursor of cancer.
adenoma.
40% of colorectal cancers have a point mutation in ___. 60% of colorectal cancers have an inactivating mutation of __.
Another important mutation in colorectal cancer involves the ___ gene, found in more than 80% of cases.
K-Ras.
p53.
Apc.
Chemotherapy affects rapidly dividing cells. List some of the side effects that can occur by these cells being affected from chemotherapy.
loss of hair (hair follicles), nausea (stomach-lining), anemia and immune dysfunction (blood-producing cells)
In CML, a reciprocal translocation occurs between chromosomes 9 and 22, causing fusion of these two proteins __ and __.
This combination protein makes highly active __, which is inhibited by Gleevec, and cell proliferation.
Gleevec takes place of ___ on Bcr-Abl.
Bcr and Abl.
tyrosine kinase.
ATP.
