Cancer Genetics I Flashcards
1
Q
list the progression of a tumor
A
Normal –> hyperplastic –> dysplastic –> neoplastic –> metastatic
2
Q
name 3 proofs of monoclonal tumors
A
- Examination of X-inactivation in cancer
- all cells from cancers have the same copy of the X inactivated
- chromosomal abnormalities of cancers
- all cells in the tumor contain the same translocation/aberration
- multiple myelomas produce a monoclonal Ig
- all myeloma cells in a patient produce the same antibody molecule
3
Q
describe protooncogenes’ role in signal transduction
A
- growth factors
- growth factor receptors
- intracellular tyrosine kinases
- G-protein/signal transduction
- transcription factors
4
Q
describe normal growth factor receptor activation vs mutant
A
- Proto-oncogenes are normal versions of genes
- mutant receptors (oncogenes) may undero automatic dimerization, even in the absence of the ligand, which then tells the cell to divide
- or receptor is truncated and always on
5
Q
describe Burkitt lymphoma
A
- Myc oncogene is fused to immunoglobin locus (t 8;14)
- myc is a transcription factor important for G1/S transition
- Level of oncogene expression is increased as myc is now under the regulation of IgH promoter because of translocation (active promoter)
6
Q
describe chronic myeloid leukemia
A
- Bcr-Abl translocation t(9;22) (Philadelphia Chromosome)
- After translocation, abl (normally a tyrosine kinase) is next to bcr which leads to a hybrid bcr-abl fusion protein
- bcr-abl fusion protein has unregulated tyrosine kinase activity and keeps telling the cell to divide
- abl stuck in active form
7
Q
describe Gleevec
A
- Gleevac (imatinib) is a drug that inhibits the bcr-abl from signalling the cell to divide
8
Q
describe mutations in Ras
A
- point mutation leads to Ras always bound to GTP (active state)
- constitutively active
- tells cell to divide
9
Q
describe oncogenesis by gene amplification
A
- Double minutes = extrachromosomal fragments of DNA
- containing an amplified region of the chromosome
- often seen in tumors where the amplified region includes an oncogene
- EGFR is often amplified as double minute chromosomes
- can be visualized with FISH probes
10
Q
describe homogenously staining regions
A
- abnormal HSRs of chromosomes in cancers often contain amplified oncogenes (can happen in any oncogenes)
- not production of mutant protein, but overproduction of protein –> uncontrolled cell division
- N-MYC amplification in neuroblastomas
11
Q
describe Wilms tumor
A
- results from Loss-of-function in the WT1 gene on ch 11
- encodes a transcription factor that is a tumor suppressor
12
Q
describe tumor suppressor genes
A
- these are genes that cause cancer when they are lost (Loss of function mutation)
- tumor suppressor genes = cell cycle control genes, apoptosis promoting genes and/or DNA repair genes
- one “good” gene is enough for cell cycle control
- need to lose the function of BOTH to get cancer
- “two hit” hypothesis
13
Q
describe the familial form of cancer
A
- 10,000 x incidence of sporadic
- often multiple tumors
- often occur earlier than sporadic
14
Q
describe the two hit hypothesis in sporadic vs familial
A
- in sporadic, 1st hit is random
- in familial, 1st hit is inherited
- therefore, more likely to cause cancer since 2nd hit is all that is needed for cancer
15
Q
describe the function of Rb protein
A
- No cyclin/Cdk
- Rb (hypophosphorylated)/E2F complex still binds DNA
- blocks transcription
- Cyclin/Cdk present
- hyperphosphorylates Rb
- Rb no longer represses E2Fs
- E2Fs activate S-phase genes (cell divides)
