Work

Genomic complexity in advanced gastric and esophageal adenocarcinomas: a case report of rare WDR11-AS1-FGFR2 fusions

Year: 2025

Type: article

Abstract: 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.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2025.1686070

Authors: Eric Mehlhaff, Dustin A. Deming, Jeremy D. Kratz, Khaldun Obeidat, Lauren Welch, Nataliya Uboha

Institutions: University of Wisconsin–Madison, University of Wisconsin Carbone Cancer Center, William S. Middleton Memorial Veterans Hospital, Guardant (United States)

Language: English

Topic: Fibroblast Growth Factor Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801