Exam 2 - lecture 11 on cancer Flashcards
What is the rate breast?
age <39 = 1/229
age 40-59 = 1/24
birth - death = 1/8
What is the rate of prostate cancer?
age <39 = 10,000
age 40-59 = 1/48
birth - death = 1/6
What are the exception of a cancers not due to old age?
cancer due to inherited mutations, Or due to exposure to high doses of mutagens, Plus certain leukemias (childhood leukemias).
What are the rate of molecular event of leukemia?
chronic - 2 to 3
acute - 3 to 4
What are the rate of molecular event of carcinoma?
in situ - 3 to 4
metastatic - 5 to 12
What are the steps in genome change?
point mutations (missens, nonsense, insertions and deletions) chromosome rearrangements (deletions, insertions, translocation ad inversions) changes in methylation pattern regulatory changes in gene expression
What is HNPCC?
HNPCC (hereditary non-poliposis colon cancer): inherited defect in mismatch repair enzyme, so patients accumulate a very high rate of genetic mutations
DESCRIBE the evolution of colon cancer
normal epithelium to early adenoma to intermediate adenoma to late adenoma t carcinoma
WHAT Are the genes involved in colon cancer?
APC, SMAD4
What is astrocytoma (glioma)
cancer of the brain
oncogenes?
Dominantly inherited (one defective allele can predispose the cell to tumor formation)
What do oncogenes do?
accelerators of cell division
STOP for Apoptosis
tumor supressors
– Recessive (Mutation in one allele predispose human to cancer, but do not cause it)
what do tumor suppressor genes do?
inhibitors of cell division
HELP for apoptosis
Types of Oncogenes
Growth factors: TGFa, EGF
Growth factor receptors: EGFR –> breast cancer
Signaling mediators: ras (colon cancer), src, AKT
Transcription factors: myc –> lymphoma
Cell cycle components: Cyclin D1
How to activate oncogene
- hyperactive protein made in normal amounts
- normal protein greatly overproduced
- nearby regulatory DNA Sequence causes normal protein to be overproduced
- fusion to actively transcribed gene greatly overproduces fusion proteins, or fusion protein is hyperactive
What happens if tumor suppressor genes are mutated?
If one copy is gone/mutated, second normal allele will function.
If both copies are gone/mutated, cancer can progress (two hit hypothesis).
Replace a single normal copy and cells return to normal (cell fusion assay).
What happens if tumor is not in the retinal cells?
if the second mutation arises in the connective tissue, osteosarcoma will occur
What is the function of Rb1 gene?
inhibitory of a gene regulatory protien
What are the ways of changing the status of oncogenes?
activating point mutations
translocation under strong promoter
amplification
overexpression
What are the ways of changing the status of tumor suppressors?
inactivating point mutations
promoter methylation
gross chromosomal deletions
underexpression
What statement describes tumors?
they are between oligoclonal and heterogeneous
How does tumor react?
Tumor reacts via expanding of pre-existing population of resistant cells, or by rapid divisions with producing of multiple clones. 99% of them non viable, but 1% is enough to win a game
How can metastasis occur?
When we push tumor to survive by producing a diverse population of cells We also push tumor to produce a cells with ability to metastasize
How does liver metastasis occur?
from colorectal and gastric carcinoma
Sequence of metastatic events
- Genesis of new vasculature (angiogenesis)
- Detachment of tumor cell from other cells; promoted by matrix degradation enzyme (MMP) and inhibited by protease and cadherins, integrins
- Invasion (entry to vessel)
Evasion of natural host defences - Arrest in small vessels
- Attachment to vessel walls
- Extravasation
- Establishment of a new growing colony
