Cancer genetics Flashcards
What are some heritable (cell-cell) changes that can occur in carcinogenesis?
driver mutations in oncogenes
driver mutations in tumour suppressor genes
epigenetic changes (do not modify DNA code eg.e methylation)
What are oncogene products involved in?
pathways that regulate growth (gain of bad function)
What do tumour suppressor gene mutations lead to?
loss of good function (normally needs loss of function in 2 alleles to have an effect)
What is a driver mutation?
alteration that gives a cancer cell a fundamental growth advantage for its neoplastic transformation
What is a passenger mutation?
has no effect on fitness of a clone but may be associated with a clonal expansion because it occurs in the same genome with a driver mutation
Are there more passenger or driver mutations?
passenger
What direct tests of the genome are there (tests that look directly at DNA/genome of cell)?
cytogenetics/karyotyping
ping FISH
PCR
next generation sequencing
What indirect tests of the genome are there (look at changes caused by mutations eg. amount of RNA/protein expressed)?
immunocytogenetics
immunohistochemistry (IHC)
expression microarray
What is cytogenetics?
study of chromosomes under a microscope, looking for broken, missing, rearranged or extra chromosomes
Describe FISH
fluorescence in situ hybridisation
molecular level
detects structural (translocation/inversion) and numerical (deletion/gain) mutations
What is PCR?
polymerase chain reaction
production of lots of a specific DNA sequence
What mutation leads to a poorer prognosis in AML?
leukaemia cells with FLT3 gene mutation give rise to a poorer prognosis and therefore may need more intense treatment or a stem cell transplant
What mutation leads to a better prognosis in leukaemia?
leukaemia cells with NPM1 gene mutation
MOA of Imatinib (Gleevec)
tyrosine kinase inhibitor
