Molecular profiling of soft-tissue sarcomas with FoundationOne Heme identifies potential targets for sarcoma therapy: a single-centre experience.

BACKGROUND

Molecular diagnosis has become an established tool in the characterisation of adult soft-tissue sarcomas (STS). FoundationOne Heme analyses somatic gene alterations in sarcomas DNA and RNA-hotspot sequencing of tumour-associated genes.

METHODS

We evaluated FoundationOne Heme testing in 81 localised STS including 35 translocation-associated and 46 complex-karyotyped cases from a single institution.

RESULTS

Although FoundationOne Heme achieved broad patient coverage and identified at least five genetic alterations in each sample, the sensitivity for fusion detection was rather low, at 42.4%. Nevertheless, potential targets for STS treatment were detected using the FoundationOne Heme assay: complex-karyotyped sarcomas frequently displayed copy-number alterations of common tumour-suppressor genes, particularly deletions in , , , and . A subset of myxofibrosarcomas (MFS) was amplified for ( = 3) and ( = 1). was mutated in 7/15 cases of myxoid liposarcoma (MLS; 46.7%). Epigenetic regulators (e.g. and ) were frequently mutated.

CONCLUSIONS

In summary, FoundationOne Heme detected a broad range of genetic alterations and potential therapeutic targets in STS (e.g. in a subset of MFS, or in MLS). The assay's sensitivity for fusion detection was low in our sample and needs to be re-evaluated in a larger cohort.