DOI: 10.1200/oa-26-00070 ISSN: 2994-9750
NRG1
Fusion–Driven Pancreatic Cancer: Real-World Detection Across a Japanese National Database and International Genomic Datasets, With an Illustrative RNA-Confirmed Case
Makoto Sugimori, Akane Hirotani, Yuichi Suzuki, Haruka Tanaka, Masanori Oshi, Yukiko Sasahara, Natsuko Takeda, Satoshi Nozaki, Haruo Miwa, Akito Nozaki, Kazuya Sugimori, Manabu Morimoto, Makoto Kudo, Satoshi Fujii, Shin Maeda
Purpose
NRG1
fusions drive oncogenic HER2/HER3 signaling and define a rare, clinically actionable subset of pancreatic cancer (PC). Zenocutuzumab, a bispecific HER2/HER3-targeting antibody, has shown antitumor activity in
NRG1
fusion–positive PC. However, real-world detection of
NRG1
fusions may vary according to assay design, target coverage, and the incorporation of RNA sequencing.
Materials and Methods
We evaluated the observed frequencies and clinicogenomic features of reported
NRG1
fusions across the Japanese national Comprehensive genomic profiling (CGP) database and international public CGP data sets spanning five CGP platforms (total N = 12,647). We additionally describe an illustrative PC case in which an
NRG1
fusion was confirmed only after RNA-based reanalysis.
Results
NRG1
fusions were identified in 7 of 12,647 cases (0.055%; 0%–0.339% across platforms), and most were
KRAS
wild-type (6/7). The index case, a 41-year-old man with invasive adenocarcinoma associated with intraductal tubulopapillary neoplasm, showed no definitive pathogenic alterations on the initial CGP report. Targeted reanalysis prompted by an 8p copy-number abnormality identified an in-frame
APP::NRG1
fusion by RNA sequencing, which was subsequently confirmed by fusion-specific reverse-transcription polymerase chain reaction.
Conclusion
NRG1
fusions in PC are rare yet clinically actionable. RNA-inclusive workflows should be considered in selected cases, particularly those without a canonical
KRAS
alteration.