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

Susanne Scheipl; Iva Brcic; Tina Moser; Stefan Fischerauer; Jakob Riedl; Marko Bergovec; Maria Smolle; Florian Posch; Armin Gerger; Martin Pichler; Herbert Stoeger; Andreas Leithner; Ellen Heitzer; Bernadette Liegl-Atzwanger; Joanna Szkandera

doi:10.1177/17588359211029125

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

Ther Adv Med Oncol. 2021 Jul 25:13:17588359211029125. doi: 10.1177/17588359211029125. eCollection 2021.

Authors

Affiliations

¹ Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria.
² Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.
³ Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Graz, Austria.
⁴ Division of Clinical Oncology, Medical University of Graz, Graz, Austria.
⁵ Diagnostic and Research Institute of Pathology, Diagnostic and Research Centre for Molecular BioMedicine, Medical University of Graz, Neue Stiftingtalstraße 10, Graz 8010 Austria.

Abstract

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 via 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 TP53, NF1, ATRX, and CDKN2A. A subset of myxofibrosarcomas (MFS) was amplified for HGF (n = 3) and MET (n = 1). PIK3CA was mutated in 7/15 cases of myxoid liposarcoma (MLS; 46.7%). Epigenetic regulators (e.g. MLL2 and MLL3) were frequently mutated.

Conclusions: In summary, FoundationOne^® Heme detected a broad range of genetic alterations and potential therapeutic targets in STS (e.g. HGF/MET in a subset of MFS, or PIK3CA in MLS). The assay's sensitivity for fusion detection was low in our sample and needs to be re-evaluated in a larger cohort.

Keywords: FoundationOne® Heme; complex karyotype; next-generation sequencing; soft-tissue sarcoma; targeted therapy; translocation-associated sarcoma.