Cancer Hetergeneity Flashcards Preview

Biology Of Cancer > Cancer Hetergeneity > Flashcards

Flashcards in Cancer Hetergeneity Deck (19)
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1
Q

Why is exome sequencing cheaper than whole genome sequencing?

A

Exomes make up the coding regions of DNA and only make up 1% of the genome
-therefore exome sequencing is cheaper and more manageable

2
Q

What are some distinct properties that cancer cells show?

A
Morphology
Metabolism
Proliferation
Metastatic potential
Gene expression
Genetic alterations
3
Q

What is inter-patient heterogeneity?

A

A subdivision of dividing cancer by histology, the driver of mutation and origin
-each patient has a unique cancer because of its genetic and genomic features

4
Q

What does inter-patient heterogeneity have consequences on and why?

A

Treatment

Only a subset of individuals bear alterations compatible with response to a drug treatment

5
Q

What are trunk and branch mutations?

A

Trunk mutations are ubiquitous, and present in the initial tumour

Branch mutations are regional and represent secondary and local mutations. Different mutations can affect the same gene (convergent evolution)

6
Q

Explain the branching evolution of a cancer

A

Trunk contains all of the original initiator events
Internal branches are the first clones to initiate heterogeneity
Terminal branches are current active clones

7
Q

What are clones?

A

A homogenous group of cells sharing the same ancestor

8
Q

Which type of mutation has a cancer cell fraction of 100% within a tumour?

A

Trunk/founder mutations

9
Q

What does it mean if a mutation has a cancer cell fraction of anything less than one?

A

The tumour cells with these mutations are sub-clones

10
Q

What shales heterogeneity?

A

The fittest clone survives, where therapy is the selective pressure

11
Q

What are the therapeutic implications of heterogeneity?

A

Get resistance

12
Q

Give an example of where resistance can be seen due to tumour heterogeneity

A

Panitumumab and cetuximab inhibit Ras, inhibiting growth of CRC
Resistance occurs due to acquisition of KRas mutations (however the mutations may have already existed)

13
Q

Give an example of how resistance can occur in melanoma

A

Vemurafenib inhibits BRAF

Get further mutations to BRAF leading to MAPK deactivation via N-Ras and over-eps region of tyrosine kinase receptors

14
Q

Give features of driver mutations

A

Implicated in omcogenesis
Confer a growth advantage in the cancer cell
Positively selected
May not be required for maintenance of the final cancer though often is

15
Q

Give features of passenger mutations

A

Do not contribute to cancer development
Found within cancer genomes because somatic mutations without functional consequences often occur during cell division but are not selected

16
Q

Give features of deleterious mutations

A

Impair cell survival

Subject to negative selections so are absent in the cancer genome

17
Q

Why is regional variation in branch mutations sometimes important?

A

A branch mutation can be a driver gene so not found in all areas of the tumour
This can affect treatment depending on where the biopsy is taken from

18
Q

Give an example of when a branch mutation is also a driver mutation

A

Lung cancer

  • BRAF is activated in the trunk
  • PIK3CA mutation only in R3
  • so a biopsy in R3 suggests treatment inhibiting PIK3 signalling
  • a biopsy elsewhere indicates BRAF inhibitors
  • therefore, R3 would likely resist this treatment
19
Q

What allows us to understand tumour heterogeneity?

A

DNA sequencing technologies eg illumine instruments, which uses sequencing by synthesis technology