[B] 1.68 Definition of tumor (oncogenes, tumorsuppressor genes) Flashcards
Definition of tumour
- Pathologic lesion
- With irreversible genetic damage in the background
- This DNA will alter a gene’s structure and/or function
- Abnormal cell proliferation
There will always be … damage during replication
DNA
Neoplasia cannot be avoided if…
The animal lives long enough
Define: Neoplasma, neoplasia
New tissue proliferation
- Neo = New
- Plasein = Compose
Define: Tumour
From main characteristics of inflammation
(4 pillars of inflammation)
Define: -oncos
“Tumour” in Greek
Define: Oncology
Discipline working with neoplasia
Carcinogenesis
Tissue proliferation
- Any tissue can be an origin
- Progressive growth with infinite proliferation ability = Immortalisation
Carcinogenesis: Self-preservation
Can be done with growth factors
- Activated by oncogenes
Carcinogenesis: Resistance to growth inhibitors
By inactivation of tumour suppressor genes
How can carcinogenesis continue against the body?
- Avoiding the immune system
- Dysregulation of the tissue’s metabolism
- Losing apoptotic ability
- Continuous angiogenesis
- Predisposition to tissue invasion and metastasis
- Sustained inflammatory processes
Define: Gene
Sequence of nucleotide in DNA/RNA encoding synthesis of a gene product
The basis of the body’s function are the…
- Autocrine signals
- Paracrine signals
- Endocrine signals
…and their effects on genes
A mutation can be…
- Somatic: In a somatic cell
- Germinal: In a gamete during gametogenesis
- Spontaneous: Error in DNA replication
- Induced: Environmental/epigenetic effect
Results of mutation can be…
- Gene mutation/point mutation: Affecting 1 gene
- Chromosome mutation: Affecting more genes
- Genome mutation: The whole genome is affected
Why mutation doesn’t always lead to oncogenesis
- Apoptosis
- The enzyme can repair the DNA error
- The error can occur in an inactive/neutral location
- Genetic mutation as an evolutionary step (adaptation)
Requirements of oncogenesis
- Numerous genetic mutations
- Preservation of replication ability
- Transmission to daughter cells
- Leads to Genetic instability
Telomerase
Enzyme that adds TTAGGG oligonucleotites to the 3’ end of the chromosome’s telomer
Telomerase activity in oncology
- The chromosome won’t be shorter during DNA replication (⇔ Deterioration with age)
- In many tumours: telomerase is reactivated
- Outcome: Immortalisation
- Treatment: Anti-telomerase therapy
Self-preservation & independence from growth factors
Main targets of carcinogenesis
- Protooncogenes
- Oncogenes
- Suppressor genes
- Stability genes
Main targets of carcinogenesis: Proto-oncogenes
- Normal genes
- Produced metabolites aid cell proliferation
Main targets of carcinogenesis: Oncogenes
- Mutant or highly expressed variants of protooncogenes
- Their function is autonomous
- Code proteins containing a structural/functional genetic error
- Oncoproteins
- Oncogene alleles are dominant
Main targets of carcinogenesis: Suppressor genes
Inhibit cell proliferation through regulation of cell cycle
Proto-oncogenes: Types
- Growth Factors (EGF, PDGF)
- Growth factor receptors (Membranous, cytoplasmic)
- Signal molecules
- Transcription factors
Damage of protooncogenes =
Gain of function
Tumour suppressor genes
- Suppressor genes containing a genetic mutation
- These mutations are recessive (except for p53)
- Both alleles need to be mutated to a phenotypic manifestation
- Damage of suppressor genes = Loss of function
Stability genes
- Members of DNA-repair system → Maintain genomic integrity
- Keep genetic variancy low
- Indirect tumor suppressors
- Mutation rate increases in other genes
Inherited cancer syndromes usually originate from…
Inherited mutation of tumor suppressor genes & stability genes
