Cancer, genetics and inherited syndromes Flashcards
Knudson’s two hit model of oncogenesis
can be hereditary or non-hereditary cancer
Non hereditary cancer
needs to have 2 hits so normal chromosomes , normal genes -1 mutation then another mutation which leads to cancer.
Hereditary cancer
individual is more susceptible to the disease as every cell in the body has the copy- only 1 sporadic
Sporadic cancer
are changes that happen during life
the mutation in hereditary is already there, what can this lead to?
risk is higher for the second hit to happen
retinoblastoma
aggressive eye cancer
what mutation is retinoblastoma initiated by?
RB1 tumour suppressor gene- located on long arm of chromosome 13q14
sign of retinoblastoma
leucorcia (abnormal white reflection from retina)
what does the RB1 gene contribute to?
the regulation of the cell cycle-return of the blastoma cells which binds to transcription factors called EF2 and stops activity of transcription factor
when the activity of transcription factor stops what happens?
stops the growth and puts break on the cell cycle-when phosphorylated by cyclins it releases the transcription factor and cell progression is allowed
what happens once phosphorylated and cyclins adds phosphate?
releases the transcription factor so cell growth continues and cell cycle continues when its mutated and cannot bind that’s why cells grow more
what 2 genes is cancer caused by?
1.BCRAC1
2.BRCA2
what are the genes BCRAC1 or BRCA2(tumour suppressor gene) involved in?
repair of the DNA and rest is sporadic
non homologous joining pathway, single stranded annealing pathway
both prone 2 errors
If there is a homologous chromosome already, they will look at that and repair the other one according to that – the pathway matches the sequence and repair it
2 main types of familial colorectal cancer
1.Familial adenomatous polyposis(FAP
2.Hereditary non-polyposis colorectal cancer(HNPCC) or lynch syndrome
what is Familial adenomatous polyposis(FAP?
has lots of lesions in the phenotypes
-gene involved EPC- is mutated in FAP cancer
what is the location of FAP cancer?
located left side of colon accounts for 1% of cancer
which chromosome is FAP cancer located?
chromosome 5
in FAP cancer what are the 3 things that chromosome 5 regulate?
1.cell proliferation
2. adhesion
3.the mutation can also be seen in sporadic cases
what is the age of onset for FAP cancer?
20-25
Hereditary non-polyposis colorectal cancer(HNPCC) or Lynch syndrome -what happens to the mutations?
DNA mismatch repair proteins
what is the age of onset for HNPCC?
40-50
What is the location of HNPCC?
this occurs at the right side of the colon
what are the mismatch repair proteins in HNPCC?
spell checkers
what protein will DNA damage pathway end up with?
microsatellites instability
what is microsatellites instability?
produce alternative sequences which are not present in original sequence , there would be a mutation in mismatched proteins so spellchecker cannot spell check what has been written which ends up with microsatellites
what is genetic testing ?
since there are germline changes it can be easily suspect change in the family or younger family members are affected , NHS labs offer genetic testing
Once the gene is identified they can offer other family members with genetic testing’sBRAC genes are big genes so take time to extract the DNA- process can take up to 3 months
Genetic counselling
gives patients right information , and what services would be beneficial for them
