Molecular basis of cancer Flashcards
what does DNA have
bases
what do bases fo
code the RNA and protein
this affects the cells
changes in DNA sequence…
If you get a change in DNA, can lead to change in mRNA then change in tRNA, then change sequence of protein (change in aa sequence)
what can DNA mutations lead to
changes in levels or function of the gene products
How is t RNA produced
1) DNA unwinds
2) mRNA produced
3) mRNA translocates into cytoplasm
4) Acts as a template at the ribosome
5) forms a sequence with tRNA
types of mutation
point
gene amplification
chromosomal translocations
point mutations
single base change
change aa
results of point mutations
framshift
- can introduce STOP codon
- change splicing
- silent mutations(no aa change)
- can lose base, moving entire sequence up (change in codon onwards)
introduction of STOP codon
leads to a truncated protein, either does not work or has an altered function
change splicing
mRNA needs to be spliced to remove introns, mutations in splice sites can either leave introns in or alter the sequence, generally stops production of protein
gene amlification
- whole regions of DNA copied more times than they should be
- normally only one gene, when the DNA copies itself can accidently copy the gene several times
- each gene will act normally and express itself, therefore there will be an overexpression
- sends lots of signals to the nucleus
chromosomal translocations
- movement of whole chromosomes
- bits of one chromosome can swap with another part
- The pairs of chromosomes should be the same
- swap between chromosome regions can lead to eg a receptor to express at different levels
- affects how cell behaves and divides
somatic mutations
occur in non germline tissues non heritable can occur anywhere accumulate mutations in life - mutations can occur in the wrong part, genome causes worse changes
gremlin mutations
present in sperm and egg
heritable
cause cancer family syndrome
de novo
can have history of germ mitations
characteristics of cancer cells
- excess proliferation without external stimuli
- loss of control mechanisms
- loss of apoptosis
- defects in DNA
- irreversible, limitless change
- acquisition of a blood supply into the tumour– angiogenesis
- invasion of surrounding structures
gees involved in cancer
oncogenes
tumour suppressor genes
apoptosis genes
mismatch repair genes
oncogenes
- apply the accelerator to cell proliferation
- promote autonomous cell growth and proliferation (no external signal prompts this proliferation in cancer)
- code for growth factors and their receptors signal transducers and cell cycle components
- normal function in controlling cell proliferation and cell division balance (proto oncogenes in normal cells, oncogenes in cancer cells)
- increased expression (activation)or activity in malignancy
tumour suppressor genes
- apply brakes to cell proliferation
- code for factors which control the cell cycle, regulate apoptosis, transcription or cell interactions
- normal function in supressing cell proliferation and maintaining tissue integrity
- loss of expression (gene deletion) or function (mutations) in malignancy
apoptosis genes
- Genes that regulate normal cell death
may see - increased activity of a gene which inhibits apoptosis
- reduced activity of genes which promote apoptosis
which gene is overexpressed In lymphomas
BCL2
apoptosis gene
mismatch reapir genes
- code for enzymes important for the repair of damaged DNA
- DNA damage common due to environmental carcinogens
- loss of expression (deletion) or function (mutation) in malignancy
- loss of repair mechanisms increases risk of mutations and activations or loss of oncogenes and tumour suppressor genes
- allows mutations to accumulate
what is proliferation
several rounds of cell divisio
two hit hypothesis
Hit 1 - inherited loss of gene on one chromosome (germline mutation) Hit 2 - sporadic loss on second chromosome leads to cancer
factors in carcinogenesisi
genetic (mutations)
environmental (e.g. UV)
chemcials (e.g. tobacco)
viruses
multistage carcinogenesis
Generally takes a lot of hits to allow the development of cancer
- cells will heal themselves generally
- until they cannot heal themselves, continuing to be exposed to factrs
(multiple genetic events from precancerous to cancer)
bowel carcinogenesis
normal hyperplastic adenoma carcinoman metastasis
epigenetic
doesnt involve changes to DNA bases but alters DNA
- chemical changes to DNA
- often occur because of environmental factors age ect
- increasingly thought to be important in cancer
- DNA methylation
- changes to histones
tumour microenvironment
contribution of other cells surrounding the tumir
all talk to the tumour
