Genetics: Genetics and Cancer Flashcards
what type of mutations is cancer largely caused by
post-zygotic - somatic mosaicism
describe the heterogeneity of cancer
the same disease can be caused by many different types of mutations
driver mutations
mutations that drive carcinogenesis
passenger mutations
mutations that are accumulated as a result of cancers instability
somatic mutations (in terms of cancer)
not inherited, mutations caused by carcinogenesis
epigenetics
the study of mutations in the gene sequence but not in the DNA sequence
what is methylation
prevents transcription by binding with histones
where does hypomethylation occur
many tumour types
where does hypermethylation occur
tumour suppressor genes
what are oncogenes activated by
proto-oncogenes that are activated by point mutations, translocations or gene amplification leading to oncogenes gaining dominant control of function mutations
as a result of mutations what might tumour cells possess
- own EC growth factors
- over expression of growth factor receptors
- continually active proteins that don’t require phosphorylation
vemurafenib MoA
inhibits continually active proteins therefore stopping proliferation
herceptin MoA
binds to receptors blocking proliferation signalling
what is the Philidelphia Chromosome
translocation between 9 and 22 that can cause leukaemia
what types of signal do normal cells rely on to regulate growth but cancer cells become unresponsive to
anti-growth signals
are tumour suppressor mutations recessive or dominant
recessive
how does hereditary Rb present
in babies with FHx
how does sporatic Rb present
in older children with no FHx
describe the 2 hit hypothesis
the first mutation increases cancer suscpetibility, the second leads to cancer
tumour suppressor genes (6)
Rb BRCA 1 BRCA 2 p53 PTEN APC
what is the normal function of tumour suppressors
supress cell division
what is the normal function of oncogenes
activates cell division
are oncogene mutations recessive or dominant
dominant
what types of mutations are tumour suppressor mutations normal caused by
point - deletions
what types of mutations are oncogene mutations normal caused by
point, gene amplification, translocations
why do cancer cells gain so many mutations
cancer cells become genetically unstable and so can acquire many mutations in order to continue growing
what is and ‘oncogenic signature’
cancer characteristics are derived from their driver mutations in oncogenes rather than their tissue of origin
what is Lynch syndrome
herediatry cancer caused by a mutation in the MLH1 repair gene
are cancers multifactorial or mendelian
usually multifactorialm 5-10% mendelian
what family features suggest an inheritable cancer susceptibility
- many 1st or 2nd relatives with cancer
- early age of onset
- many close relative with related cancer types
- bilateral tumours in paired organs
- tumours in 2 organ systems of 1 individual
what does a positive result from genetic cancer testing entail
specific mutation associated with cancer that they were looking for was found
what does a negative result from genetic cancer testing entail
the specific mutation associated with cancer was not found but individual may still develop cancer
what does a variant of unknown significance result from genetic cancer testing entail
a variant was found however lab is uncertain if it is cancer causing or not
