Tempus xT - Primary test in cancer space Flashcards
What is the test most often ordered by clinicans and considered the “Core” of Tepus Oncology tests?
xT
Why was it designed?
-To help modernize cancer care to give their patients the best options.
Components of the test:
- Tumor+normal match DNA sequencing
- Transcriptome-based RNA sequencing
- Optional IHC analysis of PD-L1 and MMR
- Structured clinical data included
xT allows clinicians to gain insight to a patient’s tumor, true or false?
True
There are two categories of information that xT generates, what are these?
- ) Therapeutically relevant infromation
2. ) Clinical trial matching
What does the therapeutically relevant information show?
- Somatic DNA variants
- Somatic RNA fusions and rearrangements
- Immunotherapy metrics
- Incidental germline findings
What about the clinical trail matching information?
- Combines molecular and clinical data
- TIME trial
Somatic mutations
occur in a single body cell and cannot be inherited.
Germline mutations
occur in gametes and can be passed onto offspring. Aka- every cell in the entire organism will be affected.
Are there add-ons for the test that a clinician can choose to opt-in for?
Yes. There is a section under the “testing options” where add-on tests can be checked.
What is NOT an element of the test?
optional FISH findings
Is the “normal match” required for Tempus to perform the test?
No - it’s just encouraged.
What is a tumor “Normal match”?
Comparing the DNA of the tumor to a patient’s “normal DNA” their “germline DNA”. Looking to see what variants are exclusive to the tumor and which are normal to that specific patient’s DNA. Sequencing them both at the same time and comparing them to each other.
When sequencing the tumor, what factors are we looking for?
- ) Genes
- ) Depth of Coverage
- ) Alterations Reported
- ) Immunotherapy Metrics
- ) Specimen Requirements
- ) Tumor content
How many genes do we sequence for the xT tumor sequencing?
648
What’s the depth of coverage?
500x
what alterations are reported?
Somatic SNV’s (somatic point mutations found in cancer tissue) / Indels CNV’s (copy # variations)
what alterations are reported?
Somatic SNV’s / Indels / CNV’s
what specimen requirements?
- Solid tumor: FFPE block + 1 H&E slide
- 10 FFPE slides+ 1 H&E slide
- 1 mL bone marrow
- 8 mL peripheral blood
what is the tumor content percent we need present in the specimen?
20% must be the tumor
how many genes?
648 sequenced, incidental germline findings reported out for 65.
Depth of coverage?
150x
alterations reported?
Incidental germline pathogenic/ likely pathogenic SNV’s, indels.
immunotherapy metrics?
N/A
Specimen requirements?
Solid tumor: 8mL blood OR 650 uL salvia
Lymphoma: Saliva
Leukemia: No normal match
Tumor content needed?
No tumor content needed since this is “normal DNA”
The normal match is not required but is strongly preferred. True or false?
True
why is this?
because the normal match allows the tumor DNA to be compared against the patient’s own normal DNA instead of a reference genome.
Does the normal match DNA improve the accuracy by reducing somatic false-positive variant’s?
Yes
Why does Tumor-Normal match matter?
- accurate somatic mutation reporting and cancer therapy matching.
- identification of provenance errors
- more accurate reporting of tumor metrics.
approx 0.2-3.5% of the time, the tumor specimen is not from the intended patient. True or false?
True
During tumor-only tests, what is the tumor being compared against?
A reference genome.
what about in the tumor-normal? what is that being compared against?
A patient’s germline DNA
Would we list a germline variant that came through on a test as a “somatic variant” on a clinical report?
No. Not on a “tumor-normal” test but we would on a “tumor-only” test.
Facts about normal match:
- not required but we do encourage it
- can be blood or saliva
- if it’s blood, it can be in a streck tube
Why does the streck tube have an advantage?
Because it can be converted to a liquid biopsy without submitting in more samples.
what does that mean in relevance to testing?
Streck tube is preferred due to the easy conversion to xF assay (liquid biopsy) if needed.
What immunotherapy metrics are automatically included?
TMB and MSI
TMB
Tumor Mutational Burden- Important marker for determining if a patient is a candidate for Immunotherapy.
MSI
Microsatellite Instability
what’s important about the TMB
- No additional sample is needed
- Reported as high if measured as 10 or greater
- Off-label indication for pembrolizumab (?)
What about MSI?
- No additional sample needed but tumor must be >30%
- Reported as high, equivocal, or stable
- On-label indication for pembrolizumab
