Tempus xF Flashcards
What does ctDNA stand for?
Circulating Tumor DNA. Specific to DNA derived from a tumor.
What does cfDNA stand for?
cell free DNA. DNA freely circulating in the bloodstream.
Are we more interested in ctDNA?
Yes, because it’s coming from cells directly impacted by a tumor.
What are CTC’s?
Circulating tumor cells. Cells that have broken off from the tumor.
True or false- Liquid biopsy is a type of assay which tests ctDNA and or CTC’s?
Yes
Explain a liquid biopsy test:
it’s a test done on a sample of blood to look for cancer cells from a tumor that are circulating in the blood or to look for DNA from tumor cells that are in the blood.
Why is CTC and ctDNA important clinically?
- screening and early detecting of cancer
- real-time monitoring of therapy
- risk for metastatic relapse
- determine at level we see which mutations and which therapies are most effective
- determining which therapies are most appropriate and if that patient will have resistance to those therapies.
Tumor shedding
Cells break off from the tumor and “shed” into the bloodstream.
1.) Tumor invasion
may happen when a tumor invades a nearby blood or lymphatic vessel.
2.) Necrosis
Due to a cell dying. Either due to treatment or naturally being released from the tumor.
3.) Apoptosis
Same thing. Cell dying
Tumor heterogeneity and clonal evolution:
different cells in a tumor have different profiles.
Minimal residual disease
detection of cancer remaining in the body during or following treatment.
clonal hematopoiesis
occurs when there is a somatic mutation in a stem cell and that mutation will appear in the blood cells which derived from that stem cell.
When does this commonly happen?
happens naturally with age, but also commonly happens in genes associated with leukemia.
Pro’s
Non-invasive
easily repeatable
minimal pain/risk in specimen collection
more comprehensive picture of disease
dynamic monitoring of disease control/resistance
potential to reveal tumor heterogeneity
Con’s
detection complicated by low concentrations
false negatives are a concern
false positives due to CHIP
quality of sample may be impacted by minor protocol deviations
no RNA analysis, no incidental germline findings.
What is Tempus xF?
a liquid biopsy test that examines both ctDNA and CTC. Both are analyzed together.
Genes analyzed?
105 genes (SNV's/indels) 7 gene rearrangements 8 copy number gains/losses
depth of coverage
5,000x (since the DNA is so small, we want to be 100% sure what we are seeing is accurate) *
immunotherapy metrics
MSI-H only (MSI-High)*
specimen requirements
- two streck tubes of peripheral blood (8.5mL)
- 4-10mL frozen plasma
- 50ng cfDNA extracted from double-spun plasma
Turnaround time
10 days from sample received
blood should be received within 72 hours of a draw
Not included
normal match incidental germline
RNA
TMB
IHC options
How it works in the lab?
1) peripheral blood sample obtained (streck)
2) centrifuged blood sample to separate out plasma, white blood cells, and platelets/ red blood cells
3) isolate cfDNA from the plasma
Streck tube- Centrifuge breakdown
Plasma- 55% of total blood
Buffy coat- <1% of total blood
Erythrocytes- 45% of total blood
what’s a huge advantage with Tempus vs. competitors:
to be able to convert from a solid tumor test to liquid biopsy.
Is there RNA in the xF test?
No. But we do show big gene rearrangements and fusions that are still detected by just seeing the DNA.
Is there normal match with this test?
No.
Included elements in this test:
- No normal match
- no MRD
- No incidental germline
- No RNA
- No TMB
What’s the point of the xF test
To determine what treatment plans are best for the patient. Designed to come up with therapeutic options for a patient with cancer.