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New research conducted by the Computational Cancer Genomics Team at the International Agency for Research on Cancer (IARC) establishes the existence of four molecular groups of lung neuroendocrine tumours, and demonstrates that each has unique etiology, clinical and epidemiological features, molecular profiles, microenvironmental niches, and evolutionary histories. The study, published today in Molecular Cancer, was conducted using the large multinational lungNENomics cohort, established by the Computational Cancer Genomics Team in 2017.
Lung neuroendocrine tumours, also known as carcinoids, are currently divided into grade 1 and grade 2 tumours. Through multi-omic integration, state-of-the-art spatial omics, and deep learning analyses, this study uncovered four molecular groups that each contained both grade 1 and grade 2 tumours, including one enriched for the highly aggressive supra‐carcinoids.
Further characterization led to the finding that molecular groups are likely to be determined early in tumorigenesis by genomic events, and that transitions between groups, although infrequent, are possible for supra-carcinoids. Deep learning models accurately identified these groups on the basis of morphology alone, outperforming current classification criteria. Finally, the study demonstrated novel molecular links between supra-carcinoids and neuroendocrine carcinomas such as small cell lung cancer.
The incidence of lung neuroendocrine tumours is rapidly increasing worldwide, but the etiology of these tumours remains unknown. In addition, the current dichotomous classification does not account for recently described molecular entities and is not sufficient for clinical management. This study makes a significant contribution towards resolving these issues by revealing novel tumour phenotypes with potential implications for prevention, classification and clinical management, and interception of high-grade transformation.
Sexton-Oates A, Mathian E, Candeli N, Lim Y, Voegele C, Di Genova A, et al.
Deep molecular profiling of lung neuroendocrine tumours and supra-carcinoids
Mol Cancer. Published online 27 August 2026;
https://doi.org/10.1186/s12943-026-02721-7
