molecular basis of cancer Flashcards
what does clonal mean?
genetic changes inherited when cells divide
what is progression?
benign tumour to malignant, metastatic tumour
3 environmental factors of getting cancer
diet, viruses, chemicals
during natural selection(evolution of cells) what are the 4 different types of mutations?
- initiating mutation
2.second mutation
3.third mutation
4.fourth mutation
what happens during initiating mutation ?
global expansion: evolution – cell that bypasses rules and regulation as single mutation gives survival advantages then the cells proliferate and grow more
what happens during the second mutation?
then it accumulates and gives rise to more cells and the second clonal expansion begins.
what happens during the third mutation?
proliferation continues and the third clonal expansion happens cells are uncontrollably, changing and growing
what happens during the fourth mutation?
it has all these uncontrollable cells also due to proliferation
in the fourth mutation, what is mild dysplasia ?
during single change is initiated cancer is not detectable but slow accumulation you can see mild dysplasia
what are the 2 things mild dysplasia can turn into?
1.moderate dysplasia
2.severe dysplasia.
what stage of cancer is situ carcinoma?
third stage of cancer
what is invasive carcinoma?
cancer has started to spread in the body
what are the 2 genes that lead to cancer?
1.oncogenes
2.protoncogenes
what are oncogenes?
mutated form of normal genes that are involved in cell growth interaction and after doses
what are protoncogenes?
normal cellular genes and include proteins which can regulate cell cycle, cell growth and cell differentiation and apoptosis
how do protooncogenes get activate and convert to oncogene?
Converted by mutation, and if 1 allele is mutated this accelerates growth (it is dominant
3 ways on how mutations happen and proton converts to oncogenes?
1.single point mutation: single nucleotide changes in DNA that is transcribed to RNA- leads to abnormal protein which is hyper active- could boost growth.
2.regulatory sequence in a mutation -multiple copies are transcribed and get overload of normal protein
3.gene amplification: gene itself is copied multiple times and transcribed to multiple RNAs and overload happens again
during activation of photo-oncogenes, what is an example of single point mutation?
-H-ras(urinary tract cancer), K-ras (highly mutated in pancreatic cancer , N-ras (skin cancer EGFR
during activation of photo-oncogenes, what are 2 examples of gene amplification?
Myc(transcription factor
-ERB2(growth factor receptors)
what 2 mutations are involved during chromosomal translocation?
1.Myc
2.Bcr
Map kinase pathway
works when growth factors bind to receptor, this pathway promotes growth and is a nutrition pathway
Ras signalling pathway
ras is an enzyme(GTPASE) – hydrolysis to GTP to GDP, if the cycle gets stopped it was keeping the RAS active. Once it is active it hydrolyses to GDP then becoming active.
what happens when mutation happens in ras signalling pathway?
the enzyme will lose the ability to hydrolase GTP to GDP so it will stay active meaning the pathways are switched for example AKT
tumour suppressor genes
supress growth. Loss of tumour suppressor function leads to cancer.
what happens during cancer when there is a gain of oncogenes
genes are switched on and when there is a loss of tumour suppressor genes which are switched off.
how are there mutations in tumour suppressor genes?
They are not dominant they are recessive- they have recessive changes -one change in tumour will not lead to cancer there needs to be two events
Knudson’s Two-hit hypothesis- loss of heterozygosity
needs to be 2 hits where the first will be single mutation and the second hit could be mutation itself or the lose part of the chromosome you have can have visitation but if there are both alleles that are affected changes will be seen -both events in gene and are affected meaning both adults are affected
what do epigenetic changes show?
methylation in one of the genes and another pair of methylation so it needs 2 hits , one change in protooncogene to be activated to oncogene.
what is main example of tumour?
suppressor gene p53 -mutated in 60% cancer
what is suppressor gene p53 called ?
guardian of the genome
what is suppressor gene p53 involved in?
DNA damage, telomere shortening, hypoxia, proliferation signalling, cell cycle arrest and apoptosis.
what is function of suppressor gene p53
modulate DNA damage , it senses DNA damage and gives cell a signal whether to repair the change or go into apoptosis- protecting cell and genome from damage that occurs.
how do mutations happen in p53 mutation?
when it is mutated there is nothing to tell the cell to that damage is there so cell cannot repair DNA and it cannot commit suicide which leads to combination of more damage.
what happens when DNA replicates?
there is mutation in the DNA version there are no spell checkers
How is Chronic Myelogenous Leukaemia (CML):blood cancer caused?
chromosomal reshuffle -9 fuses to chromosome 22 -leads to abnormal protein called BRC-ABL
when chromosome 9 cuts off it fuses with 22 chromosome, what chromosome(9) does this lead to?
a long chromosome so chromosome 22 turns into small.Chromosome 22 has BCR(brain cluster region) -when chromosome fuses to this there will be abnormal protein which enzyme to kinase will be active
Tyrosine kinase(enzyme
has advanced ETP which has an active binding site once its active it activates protein such as ras which leads to more growth
what 2 drugs to block the tyrosine kinase?
1.imatinib
2.gleevec
how can the 2 drugs block tyrosine kinase?
bind to enzyme which cannot phosphorylate the substrate so it won’t be active anymore -blocks ability of BCR-ABL kinase to phosphorylate the enzyme.
