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Updated: Sep 16, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Genomic Landscape of Resected Invasive Mucinous Adenocarcinoma of the Lung
Katsuhiro Masago1, Hiroaki Kuroda2, Katsutoshi Seto3
1Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Aichi, Japan; Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Aichi, Japan.
Background:
Invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma, accounting for 3%-10% of cases. It is often associated with KRAS mutations or, in nonsmokers, NRG1 fusions. Approximately 20% of IMAs have unclear genomic backgrounds. This study aimed to clarify the genomic etiology of these cases through a retrospective molecular analysis and RNA sequencing.
Patients And Methods:
This study analyzed 107 cases of NSCLC that were treated by surgical resection at Aichi Cancer Center from 2009 to 2023, with a focus on IMAs. For cases with unclear genomic backgrounds, RNA sequencing was conducted to identify potential driver gene alterations, and the results were compared to those of known KRAS-positive cases. Statistical analyses, including Cox regression and Kaplan-Meier analyses, were used to evaluate risk factors, recurrence-free survival, and the prognosis.
Results:
In this study, 107 cases of resected IMA were analyzed. KRAS mutations were found in 70.1% of cases, followed by NRG1 fusions (9.2%), and other mutations. A novel fusion gene, ATP6V1H::LYN, was discovered in 1 case. RNA sequencing and a gene set enrichment analysis revealed distinct molecular pathways in KRAS-positive tumors, including the activation of oxidative phosphorylation and TNFα-NF-κB signaling. Tumors with no driver gene alterations exhibited a higher frequency of copy number variations and tumor mutational burden than KRAS and NRG fusion-positive cases.
Conclusion:
IMAs are characterized by relatively higher incidences of harboring KRAS mutations and NRG fusion genes, revealing potential therapeutic targets including druggable mutations and immune-related markers, while highlighting the heterogeneous genomic background and utility of RNA sequencing.
