Lecture 2 - tumourigenesis Flashcards
What are the four main types of cancer?
Adenocarcinoma (develop in an organ or gland)
Squamous cell carcinoma (from squamous epithelial organs)
Sarcoma (connective tissue found in bones)
Leukaemia (blood, originates in bone marrow)
Lymphoma (of the lymphatic system)
Describe the general progression of cancers
A hyperplasia forms, in which cell proliferation occurs. Dysplasia (mild, then moderate) forms whereby cells start to look abnormal and have abnormal nuclei. Severe dysplasia is where abnormal cells grow in an uncontrolled fashion. Invasive SCC is where the abnormal cells invade into the surrounding tissues.
What types of cancer causing mutations occur and what do they disrupt?
Mutations in genes encoding proteins involved in regulation of cell growth and survival
this upsets the balance of proliferation/apoptosis
Somatic mutations occur in non-germline cells (90-95%)
Germline mutations occur in egg/sperm and are inheritable
How has the idea of cancer progression changed over time?
Progression was considered linear - one mutation occurred, then another, etc.
Now, it is assumed that as a tumour grows, it is subject to various selection pressures (e.g. nutrient availability) and clones containing advantageous mutations may be better at coping and will grow in clonal size.
What are the three hypotheses of cancer metastasis potential?
Clonal selection theory - tumour cells acquire mutations over time, due to selective pressure, and some of the acquired mutations may allow them to metastasise.
Predetermined genetic predisposition - metastatic potential is hardwired into early tumours, and only primary tumours with metastatic potential are preconfigured to metastasise
Host predisposition theory - tumours arising with a certain host genotype have a higher probability of metastasis
What study provides support for the host predisposition theory (hint - mice)?
Male mice genetically engineered to develop metastatic breast cancers (MMTV-PyMT) where crossed with different female mouse strains.
Depending on which strains were crossed, there was a different probability of them developing cancer.
What are the 14 hallmarks of cancer? PERRVI MIGISPEP
Proliferation, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing vasculature, activating invasion and metastasis
Deregulating cellular metabolism, evading immune destruction, genome instability & mutations, tumour promoting inflammation, senescent cells, unlocking phenotypic plasticity, non mutational epigenetic reprogramming, polymorphic microbes
