Clinicopathological Characteristics of NRG1 Fusion–Positive Solid Tumors in Korean Patients

Abstract

Purpose Neuregulin 1 (<i>NRG1</i>) gene fusion is a potentially actionable oncogenic driver. The oncoprotein binds to ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic approach for inhibiting ERBB3/ERBB2. However, the frequency and clinicopathological features of solid tumors harboring <i>NRG1</i> fusions in Korean patients remain largely unknown.Materials and Methods We reviewed archival data from next-generation sequencing panel tests conducted at a single institution, specifically selecting patients with in-frame fusions that preserved the functional domain. The clinicopathological characteristics of patients harboring <i>NRG1</i> fusions were retrospectively reviewed.Results Out of 8,148 patients, <i>NRG1</i> fusions were identified in 22 patients (0.27%). The average age of the patients was 59 years (range, 32 to 78 years), and the male-to-female ratio was 1:1.2. The lung was the most frequently observed primary site (n=13), followed by the pancreaticobiliary tract (n=3), gastrointestinal tract (n=2, stomach and rectum each), ovary (n=2), breast (n=1), and soft tissue (n=1). Histologically, all tumors demonstrated adenocarcinoma histology, with the exception of one case of sarcoma. <i>CD74</i> (n=8) and <i>SLC3A2</i> (n=4) were the most frequently identified fusion partners. Dominant features included the presence of fewer than three co-occurring genetic alterations, a low tumor mutation burden, and low programmed death-ligand 1 expression. Various clinical responses were observed in patients with <i>NRG1</i> fusions.Conclusion Despite the rarity of <i>NRG1</i> fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.