Impact of comprehensive genomic profiling on the diagnosis and clinical management of malignant mesenchymal tumours

TL;DR

This study shows that comprehensive genomic profiling helps guide treatment and diagnosis in patients with malignant mesenchymal tumors.

Contribution

The study demonstrates the clinical utility of CGP in mesenchymal tumors through actionable genomic alterations and diagnostic refinements.

Findings

25.5% of patients had potentially actionable genomic alterations suitable for targeted therapies, high TMB, or high HRD scores.

Three patients received targeted therapies based on CGP results, including CDK4, immune checkpoint, and PARP inhibitors.

CGP led to diagnostic refinement or reassignment in three cases.

Abstract

Comprehensive genomic profiling (CGP) is becoming an increasingly important tool in the clinical management of different tumours, but there is still very limited data available on its usefulness from a therapeutic point of view in mesenchymal tumours. Between January 2022 and September 2024, we performed CGP analysis with means of Oncomine Comprehensive Assay Plus (OCAplus) on 94 malignant mesenchymal tumours. The analysis covered more than 500 unique genes for single-gene and multigene biomarker insights, including tumour mutational burden (TMB) and homologous recombination deficiency (HRD). Genomic DNA and total RNA were extracted from formalin-fixed paraffin-embedded tissue blocks. Twenty-four out of 94 patients (25.5%) had potentially actionable alterations: 17 (18%) had specific genetic alterations suitable for targeted therapies, 4 (4.2%) had a high TMB (>10 mut/Mb), and 5 (5.3%) had a high HRD score >15). One additional patient had BRCA1 mutation, but the HRD score was low. Three patients received targeted therapy: one patient with a CDK4-amplified tumour (dedifferentiated liposarcoma) received CDK4 inhibitor therapy, two patients with angiosarcoma showing high TMB received immune checkpoint inhibitor therapy, and one patient with a uterine leiomyosarcoma and high HRD score received PARP inhibitor therapy. In addition, two patients with malignant phyllodes tumours received multi-thyrosine kinase inhibitor therapy. In three cases, there was refinement or reassignment of the diagnosis, based on the CGP findings. Our results demonstrate that CGP can provide useful additional information and can be beneficial in the clinical management of patients with mesenchymal tumours.

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