Fusion gene heterogeneity and kinase enrichment in high-grade serous carcinomas

Ioannis Panagopoulos; Ane Stranger; Anita Sveen; Mie Jareid; Susanne G Kidd; Katharina Bischof; Kjetil Taskén; Anne Dørum; Ben Davidson; Ragnhild A Lothe; Rolf I Skotheim; Bjarne Johannessen

doi:10.1016/j.neo.2026.101332

Fusion gene heterogeneity and kinase enrichment in high-grade serous carcinomas

Neoplasia. 2026 Jun 25:79:101332. doi: 10.1016/j.neo.2026.101332. Online ahead of print.

Authors

Affiliations

¹ Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Electronic address: ioapan@ous-hf.no.
² Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Electronic address: ane.stranger@ous-research.no.
³ Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: anita.sveen@medisin.uio.no.
⁴ Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Electronic address: mielinn@gmail.com.
⁵ Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Electronic address: s.g.kidd@ous-research.no.
⁶ Department of Surgical Oncology, Section of Gynaecological Oncology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Electronic address: katbis@ous-hf.no.
⁷ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Electronic address: kjetil.tasken@medisin.uio.no.
⁸ Department of Surgical Oncology, Section of Gynaecological Oncology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Electronic address: dorumanne@gmail.com.
⁹ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Pathology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Electronic address: ben.davidson@medisin.uio.no.
¹⁰ Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: r.a.lothe@medisin.uio.no.
¹¹ Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway; Department of Informatics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway. Electronic address: rolfis@uio.no.
¹² Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Electronic address: bjarnej@uio.no.

Abstract

Genomic instability in high-grade serous tubo-ovarian carcinoma (HGSTOC) can generate fusion genes with potential roles in tumor evolution and clinical relevance. HGSTOCs commonly disseminate prior to diagnosis, but most studies analyze only one tumor sample per patient, limiting understanding of fusion gene dynamics. Here, RNA sequencing was performed on 108 tumor samples from multiple intra‑abdominal sites in 23 patients. A consensus approach involving three fusion callers identified 170 high-confidence fusion genes present in all samples from each patient, most of which were non‑recurrent and not in-frame. Protein kinases were significantly enriched among fusion partners, and commonly retained intact catalytic domains. Several of the kinase fusion genes may have oncogenic relevance, including AKAP8L::BRD4 (recurrent in three patients), GPBP1L1::MKNK1, SPAG16::ERBB4, UGP2::MAPK4, and STRN3::PRKD1. Four fusions involved homologous recombination-related genes, including FUT10::SPIDR, RAD54B::VIRMA, RAD54L::PLXNA2, and SMARCAD1::BOD1L1. Integration of these fusion genes with other somatic alterations in homologous recombination-related genes, deficiency signatures, and germline BRCA1/2 variants increased the involvement of the homologous recombination pathway to 15 HGSTOCs (65%). Overall, HGSTOC has a heterogeneous fusion gene landscape, and multi-site sampling with consensus calling offers a robust strategy for resolving fusion profiles.

Keywords: Fusion gene heterogeneity; High-grade serous tubo-ovarian carcinoma; Homologous recombination deficiency; Kinase enrichment; RNA sequencing.