College aantekeningen Cancer Mechanisms and Immune defense (MED-B3MIN04)

LE 4 Cancer mechanisms introduction
Cancer genomics
- Identification of the full collection of mutations that contribute to the development and
progression of a cancer cell
- Sporadic and hereditary cancer

Cell proliferation
Cell differention
Apoptosis

Organismal damage (cancer)
Cellular damage (lesions)
DNA damage (mutations)

How does the cell deal with DNA damage?
- Induction of cell cycle arrest
- Induction DNA repair
- Induction apoptosis

- Base-excision repair
- Polymerase proofreading
- Mismatch repair
- Homologous recombination
- Nucleotide-excision repair
- Non-homologous end joining
- Microhomology-mediated end joining

DNA damage and p53 respons:




- Triggered when there is DNA damage
- Induce DNA repair

, Role of transcription machinery
- Transcription arrest
o DNA damage detection
o DNA repair dosimeter
o Apoptosis induction

DNA damage cancer and aging




Xeroderma Pigmentosum = global genome repair deficient
- Sunlight sensitive
- Pigmentation anomalies
- Dry skin
- Neurological anomalies
- Skin cancer (>2000x increased risk)
Werner syndrome = skin gets older faster
- Defect in pathways, increased aging
- Early onset
Hutchinson-Gilford syndrome
- Defect in apoptosis
- Increased aging

Human cancer karyotype:
- Additional copies of chromosomes