Scheipl Susanne, Brcic Iva, Moser Tina, Fischerauer Stefan, Riedl Jakob, Bergovec Marko, Smolle Maria, Posch Florian, Gerger Armin, Pichler Martin, Stoeger Herbert, Leithner Andreas, Heitzer Ellen, Liegl-Atzwanger Bernadette, Szkandera Joanna
Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria.
Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.
Ther Adv Med Oncol. 2021 Jul 25;13:17588359211029125. doi: 10.1177/17588359211029125. eCollection 2021.
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.
We evaluated FoundationOne Heme testing in 81 localised STS including 35 translocation-associated and 46 complex-karyotyped cases from a single institution.
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.
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.
分子诊断已成为成人软组织肉瘤（STS）特征描述的既定工具。FoundationOne Heme分析肉瘤DNA中的体细胞基因改变以及肿瘤相关基因的RNA热点测序。
我们评估了FoundationOne Heme检测在81例局限性STS中的应用，这些病例来自单一机构，包括35例与易位相关的病例和46例复杂核型病例。
尽管FoundationOne Heme实现了广泛的患者覆盖，并在每个样本中鉴定出至少五种基因改变，但融合检测的灵敏度相当低，为42.4%。然而，使用FoundationOne Heme检测法检测到了STS治疗的潜在靶点：复杂核型肉瘤经常显示常见肿瘤抑制基因的拷贝数改变，特别是在、、和中的缺失。一部分黏液纤维肉瘤（MFS）扩增了（=3）和（=1）。在7/15例黏液样脂肪肉瘤（MLS；46.7%）中发生了突变。表观遗传调节因子（如和）经常发生突变。
总之，FoundationOne Heme在STS中检测到了广泛的基因改变和潜在治疗靶点（如在一部分MFS中，或在MLS中）。在我们的样本中，该检测法对融合检测的灵敏度较低，需要在更大的队列中重新评估。
