GEN: Genetics of cancer Flashcards
what percentage of the human genome are genes?
1.5% -proteins, non-coding RNA
what percentage of the human genome are related sequences?
40% -introns, transcriptional reg. regions
what percentage of the human genome is repetitive DNA?
45% -centromeres,telomeres,interspersed repeats, mini/micro satellites
what 3 things can cause DNA damage?
- DNA replication errors in cell division
- UV/ionising radiation
- reactive oxygen species
what are somatic mutations?
DNA damage within a cell
what can somatic mutations cause
- cell death
- damage to non-coding DNA
- damage gene controlling cell growth
- inactive tumour suppressor gene
- active an oncogene
- create new fusion gene
what are tumours?
clonal expansions of genetically abnormal cells
what are 2 targeted therapies?
- bevacizumab - binds to VEGF reducing blood vessel formation
- imantinib - blocks tyrosine kinase activity
what 3 genes are associated with cancer predisposition?
tumour suppressor gene
- important for cell growth rate controlling, if bi-allelic loss/mutation = sporadic cancer
oncogene
- accelerate cell division, cancer arises when stuck in on mode
DNA damage-response/repair genes
- constantly repairing DNA, cancer arises due to accumulation of mutations across genome - BRCA1/BRCA2
what are 3 DNA repair mechanisms?
- mismatch repair -if insufficient, lynch syndrome ⇒ colon, ovarian, endometrial cancer
- double strand break repair - BRCA1/2
- nucleotide excision repair - XP
when are most cancer susceptibility genes dominant?
incomplete penetrance - “skip” generations where individuals inherit altered cancer susceptibility genes (not cancer)
what are the main features of cancer?
- young onset
- multiple primary cancers in same person
- same type of cancer in several relatives
- recognisable pattern of cancer in family
what are the two types of genetic mutations?
- somatic
- germline (constitutional)
what type of genetic mutations do most cancers carry?
somatic mutations not present in gremlin ⇒no inherited susceptibility for developing cancer
what are the two types of genetic tests?
- diagnostic - full screen gene (affected patient)
- predictive - specific mutation targeting that has been identified in another fam member (unaffected patient)
what is the incidence for lynch syndrome?
1 in 250
what does lynch syndrome result from?
mismatch repair deficiency
what does NICE recommend for lynch syndrome testing?
immunohistochemistry to identify tumours with MMR deficiency
what are the mismatch repair genes?
- MLH1
- MSH2
- MSH6
- PMS2
what is familial adenomatous polyposis FAP
autosomal dominant condition, 100% penetrant with polyps throughout colon
what do BRCA1/2 do?
repair double stranded DNA breaks
what is Li-Fraumeni syndrome?
rare high risk cancer disease caused by mutations of TP53
what is Peutz-Jehgers syndrome?
autosomal dominant
caused by mutations in STK11 gene
cancer predisposition
what is Cowden syndrome?
mutation of PTEN gene, developmental delay
