Molecular co-alteration patterns of RICTOR-mutant metastatic lung adenocarcinomas: a single-center cohort study.

RICTOR, a core component of the mTORC2 complex, regulates AKT signaling and has been implicated in tumor biology. While RICTOR amplification and overexpression have been reported, the mutational landscape of RICTOR and its molecular context in non-small cell lung cancer (NSCLC) remain insufficiently characterized. This study aimed to describe the prevalence and co-alteration patterns of RICTOR mutations in metastatic lung adenocarcinoma. We retrospectively analyzed 137 patients diagnosed with metastatic lung adenocarcinoma between 2018 and 2024. Genomic profiling was performed using next-generation sequencing (NGS). Pathogenic alterations were catalogued, and co-mutation patterns in RICTOR-mutant and wild-type tumors were compared. RICTOR mutations were identified in 15% (n = 20) of patients. These mutations were most frequently co-detected with EGFR (65%), KRAS (55%), and TP53 (45%) alterations. Uncommon EGFR variants, including G719X and exon 20 insertions, were enriched in the RICTOR-mutant subgroup. Additional co-occurring events included PIK3CA, STK11, KEAP1, HER2, and BRAF V600E, though at lower frequencies. Gene fusions such as ALK-EML4 and ROS1 rearrangements were rarely observed in RICTOR-mutant cases. RICTOR mutations in lung adenocarcinoma define a molecularly distinct subgroup characterized by preferential co-occurrence with EGFR, KRAS, and TP53, as well as a broader spectrum of genomic alterations. These findings support the view that RICTOR functions within complex oncogenic contexts and warrant further investigation in larger, multi-institutional cohorts.