Complex tumours genomic and transcriptomic analysis in uterine tumours resembling ovarian sex cord tumours (UTROSCT).

Background & objectives: UTROSCT is a rare entity. Most tumours behave in a benign fashion, but clinically aggressive neoplasms have been described. Our aim was to perform a comprehensive genomic and transcriptomic analysis in a series of UTROSCT to reveal clinically relevant alterations. Methods: DNA and RNA isolated from 30 UTROSCT were analysed using capture DNA NGS analysis (KAPA HyperPlus kit and a panel of 788 genes/gene parts; 2044 kbp; Roche) and transcriptome RNA-Seq (KAPA RNA HyperPrep kit; Roche), and pair-end sequenced on Next- Seq 500 or NovaSeq (Illumina). Only likely pathogenic or pathogenic (class 4/5) mutations and gene fusions were evaluated. Results: The analyses of our sample set revealed the presence of several recurrent gene fusions in the majority of the cases, including NCOA2/3. Moreover, whole transcriptome RNA-Seq revealed additional rare gene fusions such as COL6A3::FAM13B. Other alterations detected included rare class 4/5 mutations in CHEK2 and RECQL4. Conclusion: Our complex study of the molecular alterations in UTRO- SCT has revealed potentially signifcant gene fusions and genetic alter- ations in these tumours, some of which may be clinically actionable.