Pathology Flashcards
What is the percentage Likelihood of the genes for development of cancer?
488 -1% genes are implicated
What is the breakdown between it being germline or somatic?
90% are somatic mutations,20% are germline mutations that occur in the gametes and may be inherited by offspring of that cell- affecting many different types of cell
What do cancers do in normal cells?
Behave differently than normal cells in the body – related to cell division. Cancer cells multiply without any growth factors or growth stimulating protein signals.
What do mutations stimulate?
Cell survival and proliferation
What are the 2 types of mutations
dominant – gain of function- a single event creates oncogenes – overactive positive cell cycle regulators or recessive(loss of
function) – two or more mutations eliminate tumour suppression activity – inactive
negative regulators.
What does and oncogene drive?
Drives abnormal cell proliferation. They may
represent the overactive form of normal cellular genes- called proto- oncogenes or alternatively they may enter as part of a virus.A proto-oncogene may become over active and be converted into an oncogene due to mutation in coding sequence,gene amplifications or chromosomal rearrangement.
Tumour suppressors are what?
Are genes that normally inhibit proliferations and tumour development. In tumour development, tumour supressors are often lost of inactivated,usually they require 2 mutational events.Inactivation can occur through
deletion,point mutation or epigenetic changes(where the gene does not mutate but is inactivated)This may occur due to nondisjunction,giving rise to unequal mitosis, random elimination of a chromosome = recessive mutation of tumour suppressor
What are the three main types of tumour supressors?
Care takers – promote gene stability and control mutation rate (checkpoint gene p53),DNA repair gene BRCA. The gate keepers- monitor cell division and death – cell cycle Rb.Landscapers – control cellular microenvironment.
What is a stress hormone?
During treatment and after diagnosis
What are the percentages for stress hormones?
50% of cancer patients – report
anxiety,25%. Significant anxiety and 15% PTSD.
What do stress hormones result in the production of?
STRESS RESPONSE
HORMONES LIKE CORTISOL,Epinephrine NE and norepinephrine at physiological
concentrations
What can stress hormones induce?
Rapidly induce DNA damage and interfere with
DNA – damage repair process in pre- cancerous cells – which leads to cell transformation and tumorigenicity.They increase levels of proteins involved in cell cylcle regulation and progression and reduce levels of proteins that cause apoptosis and cell death
Explain the steps of tumour development in bowel cancer
cell might lose activity of a cell cyle inhibitor – events that makes cells defendants able to divide rapidly.Its unlikely that they would be cancerous,but they may form a benign tumour a mass of cells that divide too much.Overtime a mutation may atke place in one of the descendant cells,causing increased activity of positive cell cycle regulators.The mutation may not cause the cancer itself but offspring of this cell would divide even faster,creating a larger pool of cells in which a third mutation could take place.Eventually, one cell may gain enough mutations to take on characteristics of a cancer cell and therefore give rise to malignant tumour, a group of cells that divide excessively and can invade other tissue.
Explain the role of PIK3CA and that entire cascade of events
- PIK3CA mutations commonly occur concomitantly with the loss of Adenomatous polyposis coli APC.Apc has many functions,most prominent is the capacity to regulate beta- catenin mediated gene transcription in response to wnt signalling.Unbound b catenin bind to tcf/Lef gene,which transcribes for cyclin B and D.Loss of APC leads to deregulated beta catenin and hyperproliferative epithelium.
What are the 4 main properties aquired by cancer cells?
- Sustaining proliferation signalling -G1 phase,Rb protein function is lost.
- Activating invasion and metastasis: Cancer cells gain the ability to migrate to ther parts of the body
- Inducing angiogenesis – Promoting growth of new blood vessels to give tumour cells a source of oxygen and nutrients
- Resisting cell death via apoptosis- cancer cells also fail to undergo programmed cell death or apoptosis under conditions when normal calls would (eg,due to DNA damage)
