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Cancer cells_ excessive birth rate
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Cancer cells: excessive birth rate✅
What are the 4 types of genetic changes to a gene? (pathogenic
variants) which do they all lead to? - Amplification/Deletion (large
scale aneuploidy - chromosomal)
Single gene mutation (point/ small insertion -deletion )
Chromosomal translocation
Epigenetic methylation
All lead to aberrant activation or inactivation of specific genes so they
function incorrectly (at the wrong time)
✅
Amplification / Deletion- can be caused by
increased number of chromosomes (>2) from errors in cell division/
mitosis
or
Formation of “double minute“ chromosomes - extra fragment of DNA
carrying specific (onco)genes outside of the nuclear genome. Can be
reincorporated into cell chromosomes
Leads to production of MORE proteins by having extra copies of genes
Deletion can also occur during mitosis/ aberrant DNA repair leading to
loss of specific (tumor supressor genes) = less protein
✅
Partial gene deletion - case of oncogene Epidermal Growth Factor
receptor- due to deletion tyrosine kinase always dimerised which leads
to phosphorylation which leads to constant proliferation
✅
Translocation - description and case of CCND1
oncogene- Rearrangements of genetic material to juxtapose gene
promoters/regulatory elements which drives inappropriate gene
expression (activating mutation)
Translocation of CCND1 gene from Chr 11 to CHr 14 leading to IGH
enhancer element having an effect by switching on CCND1 gene leading
to excess Cyclin D1 protein which results in deregulation of cell cycle at
R point
Seen frequently in Mantle cell lymphoma
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