Genomic Alterations in Pulmonary Carcinoid Tumors: A Targeted Analysis of Gene Rearrangements and Oncogenic Mutations
Jenni Niinimäki, Soili Kytölä, Ari Ristimäki, Johanna Arola, Tiina VesterinenABSTRACT
Introduction
Pulmonary carcinoids (PCs) are rare, well‐differentiated, neuroendocrine lung tumors with limited treatment options for advanced disease, underscoring the need for targeted therapies. PCs typically exhibit a low mutational burden. Although MEN1 and chromatin‐modifier mutations are known contributors, potentially actionable alterations remain poorly characterized. To better define therapeutic opportunities, we evaluated oncogenic fusions and variants across 17 cancer‐associated genes in a large retrospective PC cohort.
Methods
Formalin‐fixed, paraffin‐embedded primary tumors from Helsinki University Hospital ( n = 119, collected between 1990 and 2020) were subjected to targeted RNA‐based fusion and variant analysis using the Archer FusionPlex Lung v2 assay.
Results
The most frequent recurrent genetic rearrangements involved ALK ( n = 5), BRAF ( n = 3), FGFR2 ( n = 3), and NTRK3 ( n = 2), each featuring diverse fusion partners. Variant analysis identified BRAF , EGFR , FGFR1 , and FGFR3 as the most frequently mutated genes, although only 2.2% ( n = 4) of all detected variants were classified as oncogenic. Notably, 66.7% of all oncogenic or likely oncogenic variants occurred in BRAF and EGFR . Oncogenic variants were identified in ALK , BRAF , EGFR , and ERBB2 . Although all FGFR1–3 variants were of uncertain significance, their frequency (34.1% of all detected variants), together with the three FGFR2 fusions, suggested that FGFR alterations may be biologically relevant in PCs.
Conclusion
Despite the typically muted genomic landscape of PCs, our study revealed a small yet therapeutically relevant subset of alterations. The findings further characterized the molecular profile of PCs and identified potentially actionable molecular subgroups. While these alterations were not associated with disease‐specific survival or metastatic status, they support consideration of molecular profiling in selected patients with advanced disease.