Genetics of Cancer Flashcards
(23 cards)
Definition of somatic mutation
DNA change after conception
Occurs in any of the cells except germ cells and is not passed on
Definition of germline (constitutional) mutation
Mutation in germ cells and can be passed onto offspring
Present in all cells
What are the risk factors associated with cancer
Age Environment Exercise and obesity Infections Genetics, family history
What are the possible consequences of somatic mutations
Damage in somatic cells, not passed onto children
Cell death
Damage in non coding/inactive DNA
Damage genes controlling cell growth
What are the possible 3 negative effects of damage in genes involved in cell growth
Inactive tumour suppressor gene => faster cell division
Activate oncogenes (missense) => gain functions and faster cell division
New fusion genes (chromosomal rearrangements) => growth advantage
Describe how a tumour can develop
Clonal expansion of genetically abnormal cells
Sporadic mutations that favour clonal expansion divide more rapidly => increased chance of more mutations
May result in a cancer that has several cells with different mutations
What 3 genes are associated with cancer predisposition and their properties
Tumour suppressor genes
Oncogenes
DNA damage response/repair genes
What are the properties of tumour supressor genes
- how can they become cancerous
- what can increase the risk of cancer here
Control cell growth rate, normally diploid
Sporadic cancer occurs with biallelic loss/mutation
Heterozygous constitutional mutation => increased risk
What are the properties of oncogenes
-how can they become cancerous
Promote cell division
Cancer occurs when stuck in ‘on mode’
What are the properties of DNA damage response/repair genes
-how can they become cancerous
Constantly repairs DNA
Cancer arises due to accumulation of mutations across genome
What are the 3 DNA repair mechanisms
Mismatch repair
Double strand break repair
Nucleotide exision repair
Describe mismatch repairs
- when would this be used
- how is DNA repaired
Replication errors (1 base errors)
- AG/CT mismatch
- Insertion/deletion
- Protein complex sees and binds to mispaired base
- DNA cut around error, mispaired nucleotide and neighbours removed, replaced with DNA polymerase
- Sealed with DNA ligase
Describe double strand break repairs
- when would this be used
- how is DNA repaired
Xrays and ionising radiation
Antitumour agents
Non homologous end joining and homologous recombination used in repair
Describe nucleotide exision repair
- when would this be used
- how is DNA repaired
UV light forming thymine dimers
Damaged bases cut out within a string of nucleotides and replaced with correct DNA
Describe the inheritance of cancer susceptibility genes
Most are dominant with incomplete penetrance
May appear to skip generations
Individuals inherit altered cancer susceptibility genes, not cancer
What are the 3 main features of familial cancers
Young age of onset of cancer
Multiple primary cancers in same person
Same cancer in many relatives/recognisable pattern in family
What is the criteria used in a cancer risk assessment
Age
-young age at diagnosis
No
- several family members affected
- multiple or bilateral tumours in 1 person
Close relatives affected
-1st degree>2nd degree>3rd degree
Patterns
- rare tumour types
- tumour associations
- histopathology
Ethnicity
-founder mutations in some populations
How can mutations affect the expression of cancer
Different mutations in different genes => different tumour risk profiles
Cancer is more likely to arise if replication rate is naturally high (epithelial cells in GI)
Double strand damage can’t be fixed due to damaged repair mech
Mutated tumour suppressor genes
What are the 2 types of genetic mutation
Somatic
- DNA change after conception
- occurs in any of the cells except germ cells so not passed on
germline (constitutional)
- mutations in germ cells and can be passed onto offspring
- present in all cells
What is the main cause of most cancers
Somatic mutations
What are the 2 types of genetic tests
When would you use them
Diagnostic
-screen gene in affected person with cancer suspected to have a familial element
Predictive
-offered to close family if genetic susceptibility confirmed by initial diagnostic test
Why would you treat constitutional cancers differently to somatic cancers
Higher chance of recurrence
Higher chance of primary cancer arising elsewhere
How would you discover cancer predisposition genes
Predisposition genes rare but have high penetrance
Common but low penetrance genes by GWAS
