What causes cancer?
- Cancer is a genetic disease at the somatic cell level
- It is a disease of mosaicism largely caused by post-zygotic mutation
- Cancer cells gain a high level of mutability → genomic instability
- Genomic instability is recognized as a key enabling characteristic of tumour development
- Tumour heterogeneity describes the observation that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential
- This phenomenon occurs both between tumours and within tumours
Driver mutations
- Mutations that drive carcinogenesis
- Two classes - oncogenes and tumour suppressors
- They determine the characteristics of a cancer (rather than its tissue of origin)
- The activation of different cancer-causing pathways gives an oncogenic signature
- A breast and an ovarian cancer (for example) can have the same pathway activated and therefore have similarities at the molecular level
- DNA analysis techniques can be used produce a molecular profile of a tumour which can guide treatment
- Any cancer is a mixture of different mutated cell lines which may respond differently to treatment
- A cell line may remain resistant to chemotherapy even if there is remission of other cell lines → relapse
Passenger mutations
- Incidental mutations that happen because the tumour is unstable
- Do not really affect cancer behaviour
Epigenetics
- The study of changes in gene expression without a change in DNA sequence
- Interaction with histone proteins
- DNA methylation
- Usually occurs on cytosine bases just before guanine bases
- Prevents transcription (leads to modification of histones)
- Deficient DNA repair genes or tumour suppressor genes due to hypermethylation → cancer
Oncogenes
Due to a genetic mutation, cancer cells may:
- Produce their own extracellular growth factors
- Overexpress growth factor receptors
- Have constitutionally active proteins that do not require phosphorylation