12) Cancer Heterogeneity Flashcards
How has next generation sequencing been useful in cancer research?
Provided us with an insight into tumour heterogeneity by multi-regional sequencing
What can whole genome sequencing be used to look for?
Structural variants, point mutations and copy number variations
What are the benefits of exome sequencing?
Only looks at coding regions
Targeted sequence can be focused in a selected target gene panel associated with malignancy
Why is there inter-patient cancer heterogeneity?
Some cancers have more mutations due to increased exposure to mutagens and due to to defects in DNA repair functions
What are the consequences of inter-patient heterogeneity for therapy?
Targeted therapies will only work in some individuals with the specific mutations that are being treated against
What is intra-patient cancer heterogeneity?
Different regions within the same tumour have different mutations
What are trunk mutations?
Are clonal mutations present in the initial tumour (founder clone)
What are branch mutations?
Are regional and represent secondary and local mutations
Describe the branched evolution of a tumour:
Start with trunk that contains the original initiator clonal events, then get internal branches that are subclones with heterogeneity. Also have terminal branches which are current active subclones
What is temporal heterogeneity?
Looking back to how the new mutations have developed from the original mutations
What is spatial heterogeneity?
Refers to the uneven distribution of various mutations across the tumour
What are actionable mutations?
Refers to a DNA change that, if detected in a patient’s tumour, would be expected to affect a patient’s response to treatment
What are driver mutations?
Confer growth advantage on the cancer cell - needed at some point during cancer development
How can heterogeneity contribute to therapeutic resistance?
Targeted therapy removes most cells but mutant subclones survive and replicate creating a population with resistant gene
What are deleterious mutations?
Mutations that impair cells survival, negatively selected in cancer genome
