BMS314 Lecture Notes - Lecture 30: Programmed Cell Death, Endocrine System, Paracrine Signalling
• Molecular basis (epigenetics)
• Molecular basis (proto-oncogenes, tumour suppressor genes)
We’ve discussed the different aetiologic agents involved in the development of neoplasia. Now
we will learn about the genes they affect and how those genes are effected.
The ultimate change that we are looking at here is alterations in how genes are expressed (e.g. if
the gene is deleted it cannot be expressed, if the genetic code is altered the product of gene
expression will be different, if a promoter is inserted upstream of a gene then the gene will be
expressed more and thus more protein product created)
These changes can be brought about either by mutations of the genes themselves (i.e. changes
to the genetic code) or by altered epigenetic expression of unchanged genes (e.g. histone
methylation and acetylation).
• Not about changes within the genetic code, but a change in how the genetic code is
expressed
• Epigenetics changes throughout your life
• Epigenetics can be inherited
Genetics and epigenetics play a crucial role in the development of tumours. Epigenetics is
defined as ‘the study of the changes in organisms caused by modification of gene expression
rather than the alteration of the genetic code itself.’ The progressive accumulation of genetic
and epigenetic abnormalities lead to disruptions in cell growth, apoptosis and DNA repair
ultimately leading to neoplasia. One of the most studied example stems from familial
adenomatous polyposis coli (APC). APC is a tumour suppressor gene that either loss or mutation
results in hyperplastic colonic epithelium. Remember that hyperplasia is a pre-neoplastic
process.
In addition to accumulative genetic abnormalities we must also consider genetic and
nonhereditary predispositions. Autosommal dominant inherited cancer syndromes including,
retinoblastoma with mutated Rb tumour suppressor gene, p53 mutations and familial cancers
including BRCA1/2. Nonhereditary disease includes chronic inflammation, most notably infection
with Helicobacter pylori leading to chronic gastritis and subsequently the production of cell
growth and survival cytokines and upregulation of cell receptor proteins.
It is important to note that DNA damage is not considered a mutation until the damaged DNA is
used as a template for daughter DNA. Typically this requires one round of replication before the
mutation is fixed into the DNA, however in some cases two rounds of replication is required.
Chromosomal instability can effect gene expression in neoplastic cells by altering the number of
copies of a gene present within that particular cell. Particular chromosomal abnormalities
including the Philadelphia chromosome where there is a relationship between chronic myeloid
leukemia and a reciprocal translocation of chromosomes 9 and 22.
https://trustedcarechiro.com/2015/06/23/epigenetics/
• Everything in your life affects this
• Factors tell histones to either open or close the DNA
o The DNA is only read/expressed when its open
Document Summary
Molecular basis (epigenetics, molecular basis (proto-oncogenes, tumour suppressor genes) We"ve discussed the different aetiologic agents involved in the development of neoplasia. Now we will learn about the genes they affect and how those genes are effected. Genetics and epigenetics play a crucial role in the development of tumours. One of the most studied example stems from familial adenomatous polyposis coli (apc). Apc is a tumour suppressor gene that either loss or mutation results in hyperplastic colonic epithelium. In addition to accumulative genetic abnormalities we must also consider genetic and nonhereditary predispositions. Autosommal dominant inherited cancer syndromes including, retinoblastoma with mutated rb tumour suppressor gene, p53 mutations and familial cancers including brca1/2. Nonhereditary disease includes chronic inflammation, most notably infection with helicobacter pylori leading to chronic gastritis and subsequently the production of cell growth and survival cytokines and upregulation of cell receptor proteins.
