The Distinct Gene Landscape of Neuregulin 1 Fusions

A retrospective study found that tumors with neuregulin 1 fusions have distinct genetic and molecular characteristics.

This retrospective study included data from 25,203 patients with solid tumors who underwent next-generation sequencing. Of all patients included, lung cancer was the most prevalent tumor type (49.4%), followed by colorectal cancer (11.1%), liver cancer (8.5%), gastric cancer (6.0%), pancreatic cancer (3.7%), sarcoma (2.6%), breast cancer (2.5%), glioma (2.1%), head and neck cancer (1.7%), cervical cancer (1.6%), esophageal cancer (1.6%), cholangiocarcinoma (1.1%), prostate cancer (0.6%), medulloblastoma (0.1%), and others.

Among all the patients, there were 49 (0.2%) identified to have NRG1 fusions. These NRG1 fusions had the highest frequency among patients with prostate cancer (0.65%), following by breast cancer (0.47%), lung cancer (0.29%), esophageal cancer (0.25%), colorectal cancer (0.17%), gastric cancer (0.13%), pancreatic cancer (0.11%), and liver cancer (0.05%). There were no NRG1 fusion events found in any of the patients with sarcoma or glioma. 

There were 36 NGR1 fusion partners identified. The most frequent partner was CD74 (29.3%), followed by NRG1-IT3 (5.2%), B3GNT6 (3.4%), IRG2BP1 (3.4%), LINC01288 (3.4%), and PTPRB (3.4%). Genomic alterations that co-occurred with NRG1 fusions were most frequently TP53 (63%), CD74 (35%), MYC (29%), CDKN2A (22%), and EGFR (22%). Additionally, there was a lack of significant tumor mutational burden (TMB) among the patients with NRG1 fusions, and all of the patients with NRG1 fusions were found to be microsatellite stable (MSS).

The study authors concluded their findings “indicate that tumors harboring NRG1 fusions have distinct genetic and molecular characteristics.” They added “understanding these differences is critical for developing personalized treatment strategies and improving the clinical prognosis of patients with these specific genetic alterations.”

Source:

Xiang S, Zheng Y, Wang M, et al. Comprehensive identification of NRG1 fusions in 25,203 patients with solid tumors. NPJ Precis Oncol. Published July 29, 2025. doi:10.1038/s41698-025-01044-y