L17: Mutations of Cancer Flashcards
Definition of cancer
Group of disorders characterised by uncontrolled cell growth, invasion, & spread (metastasis)
3 types of cancer
1) carcinnomas: occur in epithelial cells that line walls of cavities/channels
2) sarcomas: derived from mesoderm
3) adenocarcinomas: derived from glandular tissue (e.g breast)
Difference between beningn/malignant tumours
benign: grow locally/don’t invade other tissues
malignant: invade surrounding tissues & spread cancerous
Appearance of cancer cells compared to normal cells
Large no. of irregular shaped cells
Large, shaped nuclei
Variation in cell size/shape
Loss of cell features
Disorganised arrangement of cells
Evidence that cancer is a multi-step process
1) single mutation is not enough to cause cancer- function of age
2) time lag between exposure to carcinogen & development of cancer
3) examining hisopathology of intestinal epithelia
Cancer is a multi-step process
Describe the Age-dependent incident
Cancer risk increases with age due to accumultated mutation
- cells need ~6 independent rare mutations to become malignant
Hisopathology of Intestinal Epithelia
Stages of cancer progression
1) Normal colonic crypts
2) Hyperplasmia (overgrowth)
3) Polyp formation
4) Invasion & metastasis (cancer spreads)
Where does cancer originate from?
Single mutated cell (clonal origin)
Evidence that cancer originates from a single mutated cell
1) X chromosome inactivation: female cancer cells show the same inactivated X chromosome
2) Myelomas produce a single type of antidboy (blood cancer): normal B-cells produce various antidbodies, but myelomas produce only 1 type
6 key molecular events associated to cancer cells
1) growth signal autonomy: normal cells grow in response to growth factors
2) insensitivity to anti-growth signals: mutations in cancer cells interfere with inhibitory pathways
3) evading apoptosis
4) limitless replicative potential
5) ability to trigger & sustain angiogenesis
6 tissue invasion & metastasis
What are proto-oncogenes?
Encode proteins that promote cell division
- Mutated so corresponding proteins are permanently active
DOMINANT
What are tumour suppressor genes?
Inhibit cell division/induce apoptosis
- Both copies must be mutated to cause cancer
RECESSIVE
5 main classes of oncogenes
1) secreted growth factors
2) cell surface receptors
3) signal transduction components
4) DNA binding proteins
5) cell cycle regulators
5 main classes of oncogenes
Example of secreted growth factors
Small proteins mediating intercellular communication
e.g
1) Platelet derived growth factor (PDGF)
2) Insulin-like growth factor (IFG2)
5 main classes of oncogenes
Example of cell surface receptors
mutation in intracellular
4 ways proto-oncogenes become oncogenes
1) point mutation: single base change
2) gene amplification: extra copies of oncognene
3) chromosomal translocation
4) insertion into a highly active region: increase expression of oncogene
What does mutations in tumour supressor genes remove?
“Brakes” on cell division
Describe Rb gene & cell cycle control
1) Rb binds E2F (TF) to block G1-S transition
2) When Rb is phosphorylated, E2F is released, allowing cell cycle to continue
3) HPV E7 protein binds to Rb, leading to cervical cancer
Significance of p53
Stops cell cycle in response to DNA damage
- If p53 is mutated, cells divide despite DNA amage
Mutation in both alleles of p53 prevents apoptosis
