Neoplasia I Flashcards
What is cancer/neoplasia?
Disease of the genome arising from DNA alterations that dysregulate gene structure or function. These DNA alterations can be a result of genetic injury or epigenetic mechanisms.
Leads to uncontrolled purposeless cell proliferation, that continues without the inciting cause
What is the cause of cancer?
- Inherent error rate in DNA replication (takes multiple mutations for cancer to occur)
- Infectious agents, mutagenic chemicals, radiation also initiate cancer
Think of base pairs etc.
What DNA alterations cause cancer (genetic injury)?
Several types of mutation result in altered protein function:
- Single base pair mutation
- Insertions, deletions, duplications, inversions
- Structural chromosomal changes
- Gene copy number increases/decreases
What are somatic and germline mutations?
Somatic = mutation in any cell other than sperm/ovum (90%) restricted to individual cells and progeny
Germline = cells that develop into sperm/ovum and can be passed onto offspring (20%)
What DNA alterations cause cancer (epigenetic mechanisms)?
Epigenetic mechanisms regulate gene expression without any structural changes to the genome playing a role in malignant cancers - they are reversible, heritable alterations. May explain tumours associated with inflammation or foreign material but no clear pattern of mutation
What are some examples of epigenetic mechanims of cancer development?
- DNA Methylation: Silence, diminish or increase gene expression, affects tumour suppressor genes
- Histone Acetylation: DNA wound around histone proteins - unwind/tighten this binding
- MicroRNA Expression: MicroRNAs are small non-transcribed RNA molecules that bind to mRNA for post-transcriptional changes. Increasing this expression means targeting of tuour suppresot genes, reducing expression leads to oncogene overexpression
What is the normal pathway of cell proliferation?
- Growth factor released
- Binds to growth factor receptor
- Transduction
- Translation
- Cell cycle
What is a proto-oncogene?
Normal gene that becomes an oncogene following over-expression or mutation
What is a tumour suppressor gene (anti-oncogene)?
Normal genes that slow down cell division - cancerous when deletion occurs
Why does cancer require both proto- and anti-oncogenes to be mutaed in order to form neoplasms?
Proto-oncogene becomes oncogene and proliferates faster however anti-oncogene acts as the brakes and stops over proliferation of cells. Mutation = no brakes
Why is the microenvironment of a tumour important?
The tumour microenvironment is crucial in tumour growth as the tumour needs the appropriate microenvironment to deal with its increased proliferative activty such as more blood vessles, or diverse supportive ECM scaffolds.
What is the Aetiology of cancer?
Tumour incidence increases as we AGE as more inherent DNA alterations occur - more exposure to Chemical carcinogens, infectious agents and radiation carcinogenesis
Other causes include:
Hormones
Immunological factors - immunosuppresion has a role in genesis of specific tumours
Chronic inflammation factors
How does radiation carcinogenesis cause cancer?
All forms of radiation are able to initiate and promote radiation carcinogenesis - mutations caused by direct (radiant energy) or indirect (free radicals) effects
Simplify the process of multistep carcinogenesis starting with a normal cell and ending with a malignant tumour
- Normal cell goes through initiation (first cell mutation) becoming an initiated cell
- Initiated cell goes through promotion where it is ecposed to environmental factors cuasing the initiated cell to proliferate prodcuing a pre-neoplastic lesion or benign tumour
- Pre-neoplastic lesion progresses via more mutations into a malignant tumour
How does the initiation stage of cancer formation occur?
- Irreversible genetic change caused by mutagenic initiator
- Initiated cells seem morphologically normal
- Yet the mutations give them a growth advantage so they respond more quickly to mitogenic signals or resistance to apoptosis-inducing stimuli
