FGFR2-fusions define a clinically actionable molecular subset of pancreatic cancer

Leah Stein; Karthikeyan Murugesan; Julie W Reeser; Zachary Risch; Michele R Wing; Anoosha Paruchuri; Eric Samorodnitsky; Emily L Hoskins; Thuy Dao; Amy Smith; Dat Le; Melissa A Babcook; Yi Seok Chang; Matthew R Avenarius; Muhammad Imam; Aharon G Freud; Sameek Roychowdhury

doi:10.1038/s41698-024-00683-x

FGFR2-fusions define a clinically actionable molecular subset of pancreatic cancer

NPJ Precis Oncol. 2024 Sep 17;8(1):207. doi: 10.1038/s41698-024-00683-x.

Authors

Leah Stein^#^{1

2}, Karthikeyan Murugesan^#³, Julie W Reeser¹, Zachary Risch¹, Michele R Wing¹, Anoosha Paruchuri¹, Eric Samorodnitsky¹, Emily L Hoskins^{1

2}, Thuy Dao¹, Amy Smith¹, Dat Le¹, Melissa A Babcook¹, Yi Seok Chang¹, Matthew R Avenarius^{1

4}, Muhammad Imam⁵, Aharon G Freud^{1

4}, Sameek Roychowdhury^{6

7}

Affiliations

¹ Comprehensive Cancer Center and James Cancer Hospital, The Ohio State University, Columbus, OH, USA.
² Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, USA.
³ Foundation Medicine Inc, Cambridge, MA, USA.
⁴ Department of Pathology, The Ohio State University, Columbus, OH, USA.
⁵ Florida Cancer Specialists, Orlando, FL, USA.
⁶ Comprehensive Cancer Center and James Cancer Hospital, The Ohio State University, Columbus, OH, USA. Sameek.Roychowdhury@osumc.edu.
⁷ Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. Sameek.Roychowdhury@osumc.edu.

^# Contributed equally.

Abstract

Genomic alterations in fibroblast growth factor receptor (FGFR) genes are present in a small number of metastatic pancreatic ductal adenocarcinomas (PDAC) and may represent an emerging subgroup of patients likely to benefit from FGFR targeted therapies. Here we present four FGFR2 fusion-positive metastatic PDAC patients who exhibited durable responses or disease control to FGFR kinase inhibitors. Utilizing our custom FGFR focused cell-free DNA assay, FGFR-Dx, we serially monitored variant allele fractions of FGFR2 fusions during FGFR inhibitor treatment and observed dynamic changes correlating with clinical responses. Genomic analysis of 30,229 comprehensively profiled pancreatic cancers revealed FGFR1-3 fusions in 245 cases, an incidence of 0.81%. FGFR fusions were generally mutually exclusive from other known oncogenes. Our findings provide clinical evidence for identifying and treating FGFR2 fusion-positive PDAC patients with FGFR targeted therapy.

Abstract

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