What does my FoundationOne report mean?
A FoundationOne report lists the genomic alterations found in your tumor, sorted into those with an approved therapy, those with a therapy approved in another tumor type, and those with clinical trial relevance. It also reports TMB, MSI status, and sometimes genomic signatures. The therapy list is generated by an algorithm, not tailored to your history.
The four things on page one
Most patients are handed the report and told the summary. The four items that actually drive decisions are the reported alterations, the tumor mutational burden, the microsatellite instability status, and the list of variants of unknown significance that most summaries skip entirely.
- Genomic alterations: the mutations, fusions, amplifications, and deletions detected
- TMB: mutations per megabase, relevant to immunotherapy response likelihood
- MSI status: stable, low, or high, with MSI-High opening immunotherapy pathways
- Variants of unknown significance: not actionable today, sometimes reclassified later
Why the therapy list is a starting point, not a plan
The therapies printed alongside each alteration come from a matching engine. It does not know which lines of therapy you have already had, which drugs you failed, what your organ function looks like, or which trials near you are actively enrolling. It also does not weigh alterations against each other when two point in different directions.
The interpretive work is deciding which alteration is the driver, whether co-occurring mutations predict resistance, and whether the trial options listed are still open. That is the gap a molecular case review fills.
What a report does not tell you
Negative does not always mean absent. Coverage depends on tissue quality and tumor content, and some fusions are missed on DNA-only panels, which is why RNA fusion testing is sometimes added. If a result contradicts the clinical picture, that discrepancy is worth resolving before it drives a treatment decision.
Related questions
What is a variant of unknown significance?
A detected change with no established clinical meaning yet. Some are later reclassified as significant, which is why re-reviewing older reports occasionally surfaces new options.
Can a FoundationOne report be re-analyzed later?
Yes. The underlying data does not change, but the literature does. Reports two or more years old frequently contain alterations that now have approved or trial-stage therapies.
Which is better, tissue or liquid biopsy?
They answer different questions. Tissue gives the fuller picture when adequate sample exists; liquid captures tumor DNA circulating in blood and is useful when tissue is unavailable or when tracking change over time.
Reviewed 2026-08-13 by Kim Lockheimer, PhD, DFM.