Analysis of clinical and genomic features in a Chinese cohort with NRG1 variations: a retrospective study

Neuregulin 1 (NRG1) fusions are recognized oncogenic drivers in non-small cell lung cancer (NSCLC), yet, the clinical and genomic features of other types of NRG1 alterations are still rarely reported. This study aimed to characterize the associated clinicogenomic profiles for NRG1 fusions and single nucleotide variants (SNVs) in a Chinese NSCLC cohort.

We retrospectively analyzed next-generation sequencing (NGS) data from 3,132 Chinese NSCLC patients and investigated NRG1 alterations and their correlations with clinical characteristics, co-mutation landscapes, and treatment outcomes.

NRG1 fusions and SNVs were detected in 0.2% (6/3,132) and 0.7% (22/3,132) of patients, respectively. Fusions were enriched in invasive mucinous adenocarcinoma (IMA) and associated with co-mutations in KRAS and EGFR. CD74 was the main fusion partner (50%). However, SNVs were significantly associated with male sex, smoking history, squamous cell histology, high tumor mutational burden, and mutations in epigenetic regulator genes, including SETD2, SMARCA4, KMT2A, and ARID1A. No hotspot mutation sites in NRG1 were found. The overall objective response rate of all NRG1-positive patients reached 73.9% after they received existing therapies. Operable patients achieved sustained remission for 6 to 29 months after surgery. Chemotherapy plus immunotherapy was highly effective for advanced-stage NRG1-positive patients.

This study revealed the distinct clinicogenomic landscapes of NRG1 fusions and SNVs in NSCLC. These findings emphasize the important role of molecular profiling for precision diagnosis and individualized treatment of NSCLC.