Endometrial stromal tumors are rare lesions with a diverse morphology, which may make achieving the correct diagnosis challenging in some cases. We report a case of a uterine mesenchymal tumor diagnosed as endometrial stromal nodule with a peculiar whorled morphology and GREB1::CTNNB1 fusion confirmed by transcriptome RNA sequencing. The tumor was sharply demarcated, lacked invasive growth, and had benign behavior, as the patient remained without disease recurrence 15 years later. Immunohistochemically, the tumor cells showed diffuse nuclear expression of beta-catenin, confirming the activation of the beta-catenin pathway. Our case represents only the 4th reported case of CTNNB1-rearranged endometrial stromal tumor with extensive whorling. The biological nature of uterine tumors characterized by whorled morphology and rearrangement of CTNNB1 is not yet clear, which underscores the importance of genetic profiling for accurate diagnosis and potential targeted therapies in malignant cases.

• Klíčová slova
• ESN, Endometrial stromal tumors, GREB1, GREB1::CTNNB1 fusion, Uterine mesenchymal tumors,
• MeSH
• beta-katenin * genetika   MeSH
• endometriální stromální nádory * genetika   patologie   MeSH
• fúze genů MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádorové proteiny * genetika   MeSH
• nádory endometria * genetika   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• beta-katenin * MeSH
• CTNNB1 protein, human MeSH Prohlížeč
• GREB1 protein, human MeSH Prohlížeč
• nádorové biomarkery * MeSH
• nádorové proteiny * MeSH

The subset of ovarian cancer (OC) diagnosed ≤ 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline cancer predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis in 123 early-onset OC-patients compared to histology/stage-matched late-onset and unselected OC-patients, and population-matched controls. Only 6/123(4.9%) early-onset OC-patients carried a germline pathogenic variant (GPV) in high-penetrance OC-predisposition genes. Nevertheless, our comprehensive germline analysis of early-onset OC-patients revealed two divergent trajectories of potential germline susceptibility. Firstly, overrepresentation analysis highlighted a connection to breast cancer (BC) that was supported by the CHEK2 GPV enrichment in early-onset OC(p = 1.2 × 10-4), and the presumably BC-specific PRS313, which successfully stratified early-onset OC-patients from controls(p = 0.03). The second avenue pointed towards the impaired immune response, indicated by LY75-CD302 GPV(p = 8.3 × 10-4) and diminished HLA diversity compared with controls(p = 3 × 10-7). Furthermore, we found a significantly higher overall GPV burden in early-onset OC-patients compared to controls(p = 3.8 × 10-4). The genetic predisposition to early-onset OC appears to be a heterogeneous and complex process that goes beyond the traditional Mendelian monogenic understanding of hereditary cancer predisposition, with a significant role of the immune system. We speculate that rather a cumulative overall GPV burden than specific GPV may potentially increase OC risk, concomitantly with reduced HLA diversity.

• Klíčová slova
• Early-onset, Germline whole exome sequencing, HLA, Mutation burden, Ovarian cancer, Polygenic risk score,
• MeSH
• checkpoint kinasa 2 genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory vaječníků * genetika   MeSH
• studie případů a kontrol MeSH
• věk při počátku nemoci * MeSH
• zárodečné mutace * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• checkpoint kinasa 2 MeSH