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CASE REPORT article

Front. Oncol.

Sec. Cancer Molecular Targets and Therapeutics

Genomic Complexity in Advanced Gastric and Esophageal Adenocarcinomas: A Case Series of Rare WDR11-AS1-FGFR2 Fusions

Provisionally accepted
Eric MehlhaffEric Mehlhaff1Dustin DemingDustin Deming1,2Jeremy KratzJeremy Kratz1,2,3Khaldun ObeidatKhaldun Obeidat4Lauren WelchLauren Welch5NATALIYA UBOHANATALIYA UBOHA2,6*
  • 1Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, United States
  • 2University of Wisconsin-Madison Carbone Cancer Center, Madison, United States
  • 3VA Medical Center Madison, Madison, United States
  • 4Department of Hospital Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, United States
  • 5Guardant Health Inc, Redwood City, United States
  • 6Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin-Madison, Madison, United States

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Fibroblast growth factor receptor 2 (FGFR2) alterations represent an emerging therapeutic target in gastroesophageal adenocarcinoma (GEA). Although FGFR2 amplifications and overexpression have been associated with poor prognosis and therapeutic resistance, the clinical significant FGFR2 fusions , which are exceedingly rare, is unknown. Herein we describe two cases of advanced gastroesophageal and gastric adenocarcinomas characterized by aggressive disease course, rapid progression despite standard first-line chemoimmunotherapy, and the presence of high-level FGFR2 amplification with concurrent WDR11-AS1–FGFR2 fusion detected by circulating tumor DNA (ctDNA) analysis. These cases highlight the genomic complexity and aggressive behavior of FGFR2-driven GEA, underscored by coexisting genetic alterations. The findings emphasize the importance of comprehensive genomic profiling, including both tissue and liquid. in order to capture intratumoral heterogeneity and evolving molecular events. Further investigation of FGFR2 fusion biology and combinatorial therapeutic strategies is warranted to address the clinical challenge of biomarker overlap and treatment resistance in GEA.

Keywords: gastric cancer, biomarker, WDR11-AS1, liquid biopsy, FGFR2 fusion

Received: 14 Aug 2025; Accepted: 11 Nov 2025.

Copyright: © 2025 Mehlhaff, Deming, Kratz, Obeidat, Welch and UBOHA. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: NATALIYA UBOHA, nvuboha@medicine.wisc.edu

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material