Mechanisms of neoplasia 1 Flashcards
Definition of neoplasia
abnormal proliferation of cells, A neoplasm= abnormal mass of tissue that occurs as a results of abnormal cellular proliferation
What happens in a low grade neoplasm?
-Cells begin to proliferate abnormally but structure of tissue is maintained
What happens in a high grade neoplasm?
Structure of tissue is affected, at this stage cells have to undergo specific abnormal mutations for the tumour to begin invasive
What happens in an invasive carcinoma?
Cancer cells invade neighbouring tissue. They will eventually spread to local blood/ lymph systems.
What is the difference between monoclonal and polyclonal tumours?
Monoclonal= originate from a single cell. The mutations began in 1 single cell. Normally occurs in leukemia Polyclonal= originate from mutations that occured in more than one cell. Often the case for solid tumours. Often more difficult to find effective treatments for.
What forms the risk of an individual getting cancer?
Combination of genetic factors and environmental factors
Give examples of chemical and physical carcinogens
- Chemical: coal tars, some hdrocarbons (PAHs), asbestos
- Physical: ionizing radiation (X-rays, UV)
What is a point mutation?
change of one or several bases in DNA sequence
- Nonsense: truncated protein
- Missense: protein with altered function
What is a chromosomal alteration?
change in composition of a chromosome of change in the chromosome number
-Deletion/ insertion/ translocation, amplification
What is epigenetic regulation?
It occurs via different modifications of histones and methylation of DNA in the chromatin
-e.g. changes in the histone tails and other structures of how DNA is compacted. These can be caused by environmental factors.
What is the multiple hit hypothesis?
That one mutation is not normally efficient enough to cause cancer. Multiple hits (alterations) are normally needed.
- However some families can carry specific genes which code for mutations that are enough to cause cancer.
Which 2 classes of genes are involved in tumours?
- Oncogenes (promote cell proliferation)
- Tumour supppressor genes ( prevent aberrant cell proliferation)
What converts proto-oncogenes into oncogenes?
-Gain of function such as over expression or sustained activity
Which oncogene is caused by gain of function by mutation?
Ras and MAPK
Which oncogene is cause by gain of function by translocation?
c-MYC
Describe how Ras can be oncogenic
- Can give continuous proliferation of cells, controls the MAPk pathway.
- Can use inhibitors to stop the cancer growing
Describe the mechanisms c-MYC uses as an oncogene
- MYC is the chromosome, it can translocate onto another chromosome where there is an Ig gene which is very overactive, MYC is then expressed constantly which activates non stop proliferation.
- The Ig is always active.
How can growth signals be oncogenic?
- Deregulation of receptor signalling occurs
- Over expression of receptors on membrane
- Alteration in protein structure (signalling without the ligand)
What are tumour suppressor genes?
They are the gate keepers of cancer, when they lose their function this induces cancer.
e.g. p53 (apoptosis), p16 and p21 (cellcycle inhibitors), DNA repair
What does a stable/ active p53 lead to in the cell cycle?
Can either arrest it or trigger apoptosis if the cell is faulty. If p53 is faulty then DNA repair genes can also be tumour suppressors.
What is the importance of telomerase enzyme?
-It is expressed by cancer cells, this means they maintain long telomeres and effectively become immortal.
