Potential Therapeutic Targets for Patients With Invasive Mucinous Adenocarcinoma

According to a study, invasive mucinous adenocarcinomas (IMA) exhibit higher incidences of KRAS mutations and NRG fusion genes.

IMA is a rare subtype of lung adenocarcinoma which accounts for approximately 3% to 10% of cases. While IMA is usually associated with KRAS mutations and NRG1 fusions, particularly among non-smokers in the case of the latter, about 20% of cases have an unclear genomic background.

In this study, there were 107 cases of non-small cell lung cancer (NSCLC), included with an focus on IMA, sourced from patients who underwent surgical resection at the Aichi Cancer Center between 2009 and 2023. RNA sequencing was done for cases with unclear genomic backgrounds, with results compared to confirmed KRAS-positive cases. Risk factors, recurrence-free survival, and prognoses were evaluated.

The most common driver gene alterations found were KRAS mutations in 70.1% of all cases, followed by NRG1 fusions in 9.2% of cases. There was 1 case with a novel fusion gene identified: ATP6V1H::LYN. Through RNA sequencing and gene set enrichment analysis, there were distinct molecular pathways identified in the KRAS-positive tumors. These included the activation of oxidative phosphorylation and TNFα-NF-κB signaling. There was a higher frequency of copy number variations and tumor mutational burden among cases with no driver gene alterations when compared with KRAS- and NRG1 fusion-positive cases.

Study authors concluded this higher potential for KRAS mutations and NRG fusion genes among patients with IMA shows “potential therapeutic targets including druggable mutations and immune-related markers, while highlighting the heterogeneous genomic background and utility of RNA sequencing.”

Source:

Masago K, Kuroda H, Seto K, et al. Genomic landscape of resected invasive mucinous adenocarcinoma of the lung. Clin Lung Cancer. Published online: June 13, 2025. doi: 10.1016/j.cllc.2025.06.004